RARECast: Recent Episodes

RARECast

RARECast is a Global Genes podcast hosted by award-winning journalist Daniel Levine. It focuses on the intersection of rare disease with business, science, and policy.

Cystic fibrosis is a rare disease that has been an area of significant innovation. New therapies have provided life-changing treatments for most patients, but about 10 percent of people with the condition don’t benefit from these treatments because of the specific mutations underlying their condition. We spoke to Jamie Chang, senior medical director at the contract research organization Rho, about the advances that have been made to treat cystic fibrosis, the treatment gap that remains, and what’s working its way through the pipeline that may change that.

At 41, Bill Potts received a diagnosis of thyroid cancer. He listened to the recommendations from his primary care physician and didn’t seek out a second opinion. It was only six months later, during a follow up visit when his doctors wanted to repeat his treatment with radioactive iodine that he began to ask questions and started to advocate for himself. He now says he would likely be dead had he not sought out a second opinion at that time. He’s since learned a lot about advocating for himself with cancer as he’s been diagnosed six times with cancer. He’s taken what he’s learned from his experiences and written Up for the Fight, a guide for newly diagnosed cancer patients, family members, and caregivers. It provides not only critical advice on dealing with the mental aspects of the disease, but also lots of practical advice about navigating the healthcare system, insurance companies, and treatments that could only come from lived experience. We spoke to Potts about why it’s essential for patients to learn to advocate for themselves, how to navigate the mental and emotional aspects of the disease, and why it’s important to stay motivated and celebrate small achievements along the way.

Regulatory T cells target systemic inflammation and neuroinflammation, but when they fail to function properly, they can drive serious health conditions including neurodegenerative, metabolic, and autoimmune diseases. Coya Therapeutics is developing a pipeline of therapies designed to restore the ability of Tregs to modulate the immune system and reduce inflammation. The company’s lead experimental therapy is a combination of two biologics designed to treat ALS by boosting anti-inflammatory Tregs while suppressing other immune cells that drive inflammation. We spoke to Howard Berman, chairman and CEO of Coya, about the role of inflammation in neurodegenerative conditions, Tregs, and the company’s experimental therapy to treat ALS.

Cristóbal Baca and Ana Ortiz came to New Mexico in 1600. Today, they have as many as 5 million descendants. A four-year effort involving community volunteers and workers, medical professionals, researchers, and families across New Mexico unraveled what had been a long-standing medical mystery. It turns out Baca and Ortiz are the source of a founder mutation for cerebral cavernous malformation, a sometimes-hereditary illness that causes the development of abnormal blood vessels in the brain and spinal cord and is potentially fatal. Some 30,000 New Mexicans carry the mutation. We spoke to Connie Lee, president and CEO of the Alliance to Cure Cavernous Malformation, about the Baca Family Historical Project, how her organization leveraged partnerships with community leaders to identify people with the condition, and how the organization used a novel approach to engage people and improve their access to testing and care.

In June, the National Institutes of Health’s National Institute of Neurological Disorders and Stroke made a five-year, $22.8 million grant to a group led by The Jackson Laboratory to develop gene-editing therapies for four rare, neurological conditions. The use of a platform approach to develop therapies for multiple indications follows other efforts on going at the National Institutes of Health in the area of gene therapies. We spoke to Steve Murray, associate professor at The Jackson Laboratory, about the promise of gene-editing, the work being done under the grant, and why the work could have broad implications for treating rare genetic neurological conditions.

CDKL5 deficiency disorder (CDD) is a serious and rare, genetic condition characterized by early onset and difficult to control seizures, as well as severe neuro developmental impairment. Last year, the U.S. Food and Drug Administration approved Marinus Pharmaceuticals Ztalmy to treat seizures associated with CDD, the first FDA approved therapy for the condition. Marinus is seeking to expand the use of Ztalmy in other seizure disorders including tuberous sclerosis complex and Lennox-Gastaut syndrome. We spoke to Alex Aimetti, chief scientific officer of Marinus, about Ztalmy, how it works, and the efforts to expand its use to other seizure disorders.

Clothing is both functional and a means of self-expression, according to Open Style Lab, a nonprofit that works with designers, engineers, and occupational therapists to create clothing that addresses the needs of people with disabilities. Earlier this year, as part of Genentech’s SMA My Way initiative, Open Style Lab and the SMA community joined forces for New York’s Fashion Week to feature the Double-Take fashion show in the hopes of increasing the visibility of people with disability and championing adaptive fashion. We spoke to Yasmin Keats, executive director of Open Style Lab, about her organization’s efforts to promote the design of adaptive fashion, the impact it can have on work and other opportunities for people living with disabilities, and how it is helping to change the fashion industry.

Pulmonary arterial hypertension is a rare and progressive condition characterized by high blood pressure in the arteries of the lungs due to their narrowing or a blockage. This causes the heart to work harder to pump blood and leads to heart failure, the need for lung transplantation, and death. Aerami is developing an inhaled form of the targeted cancer therapy imatinib as a treatment for PAH. We spoke to Josh Ziel, chief operating officer and interim CEO of Aerami, about pulmonary arterial hypertension, the company’s experimental therapy to treat the condition, and its efforts to build a pipeline of therapies that make use of its proprietary inhalation technology.

The search for a diagnosis can take many years and requires going from doctor to doctor without finding a definitive answer for people with ultra-rare conditions, atypical presentations, or yet-to-be discovered diseases. A group of undiagnosed and ultra-rare diseases patients and their family members, medical providers, and advocacy partners launched the Undiagnosed Diseases Network Foundation to improve access to diagnosis, research, and care for people with undiagnosed diseases. We spoke to Amy Gray, CEO of the UDNF, about its work, its relationship with the National Institutes of Health-backed Undiagnosed Disease Network, and the organization’s top priorities.

Our interactions with the environment can have unexpected effects on our genes and trigger a biologic response that leads to the onset of disease. These interactions can also leave a measurable record in what’s referred to as the exposome. LinusBio, which emerged from the exposome laboratory at Mount Sinai Health System, has developed a test for autism that relies on analyzing a single strand of hair. The company said the test is capable of diagnosing autism at birth. We spoke to Manish Arora, founder and CEO of LinusBio, about the exposome, how the company’s test for autism works, and how this opens the potential for early interventions.

Congenital pseudarthrosis of the tibia is a rare condition that can cause spontaneous fractures, mobility problems, and impede proper growth. It is treated surgically, but because the bone often breaks again, it can lead to amputation. Novadip is developing an autologous cell therapy to allow tissue regeneration of large bone defects. We spoke to Denis Dufrane, co-founder and CEO of Novadip, about the rare pediatric bone disorder, the company’s cell therapy to address the condition, and how it works.

The transformational potential of AAV gene therapies has been limited by challenges of delivering genetic material to the cells where they need to go, gene expression, immunity, and the complexity of manufacturing them. Apertura Gene Therapies is seeking to simultaneously engineering AAV capsids, genetic regulatory elements, and payloads to overcome these limitations. We spoke to Joseph La Barge, CEO of Apertura, about its platform technologies, how they work, and the potential for next-generation gene therapies to transcend the limits of first-generation AAV therapies.

In October, Alnylam said it would halt development of a therapy for a rare eye disorder to evaluate the impact of the Inflation Reduction Act. The decision is a reflection of the unintended consequences that policies can have on rare disease drug development. We spoke to Amanda Malakoff, executive director of the Rare Disease Company Coalition, about the policy landscape for rare disease therapies, unfinished business from the recent passage of a lean Prescription Drug User Fee Act, and policy priorities for 2023.

In December 2020, Ovid Therapeutics’ experimental therapy OV101 for the rare, neurodevelopmental condition Angelman Syndrome failed to meet its primary endpoint in a phase 3 clinical trial and the company chose to discontinue development. But rather than let the data from the study languish on the shelf, Ovid made the decision to contribute it to the Angelman Syndrome Foundation’s LADDER database. We spoke to Ovid CEO Jeremy Levin and Angelman Syndrome Foundation CEO Amanda Moore, about the LADDER database, Ovid’s decision to contribute its data to it, and why the two believe other drug developers should take similar steps to share their data with patients and researchers to advance the understanding of rare diseases.

Fabry disease is a progressive disorder that affects organs throughout the body including the heart, kidneys, and nervous system. People with the condition may suffer for years before obtaining a diagnosis. Jack Johnson, who co-founded the Fabry Support and Information Group, traced Fabry disease back more than five generations in his family. We spoke to Johnson about his own experience with the condition, his journey into advocacy, and a recent externally-led Patient-Focused Drug Development meeting to help regulators and drug developers understand the need for new therapies to address the challenges of living with the disease.

Racial disparities in care and outcomes have been well documented but the problems can be particularly acute in cases of rare, genetic diseases. One example of this is the rare blood cancer cutaneous T-cell lymphoma. African Americans are twice as likely as people of European or Asian descent to develop CTCL, are typically diagnosed with more advanced disease, and have a lower survival rate from the condition. Kyowa Kirin North America, which produces the CTCL treatment Poteligeo, is working to address racial disparities to improve the diagnosis, care, and outcomes of African American patients with CTCL. We spoke to Kyowa Kirin Vice President of Public Affairs Lauren Walrath and Co-Leader of the Immune Cell Regulation and Targeting Program at the Sidney Kimmel Cancer Center at Jefferson Health Pierluigi Porcu, about CTCL, the disparities in care and outcomes for African Americans with the condition, and what they are doing to address that.

Just three years after Children’s Mercy Research Institute launched its Genomic Answers for Kids program, it reported that it had hit the milestone of providing 1,000 rare disease diagnoses to families. One reason for the success of the GA4K program has been the use of advanced genomic sequencing that captures the full genome and methylome to reveal part of the human genome that has never been clinically tested to interpret changes beyond the genetic code. We spoke to Tomi Pastinen, director of the Genomic Medicine Center at Children’s Mercy Kansas City, about the GA4K program, how new sequencing technology is allowing it to diagnose rare disease patients who previously were undiagnosable, and how it has the potential to alter the diagnostic odyssey for patients with rare, genetic diseases.

Health Storylines is a patient-driven, digital platform for people to track and manage their health, but it is also a tool to enable drug and device developers to conduct decentralized clinical trials and gather real-world evidence. Alira Health expanded its digital health offerings with Health Storylines through its acquisition of Self Care Catalysts at the start of 2022. We spoke Gabriele Brambilla, CEO and co-founder of Alira Health, about how the technology provides patients with greater control over their own health, how it is using it to drive decentralized clinical trials and the integration of real-world evidence in the drug development process, and the potential to leverage its Health Storylines platform to answer research questions outside of a traditional clinical study.

The rare disease patient advocacy organization Global Genes and the rare disease patient data sharing platform RARE-X have agreed to merge, a move they say will provide next-generation rare disease advocates the tools and resources they need to accelerate their drive for treatments. Charlene Son Rigby, CEO of RARE-X, will become CEO of the combined organization. We spoke to Son Rigby about the merger, the convergence of her personal and professional lives, and how the combination of the two organization will provide next-generation rare disease advocates the tools and resources they need to accelerate their drive for treatments.

Michael Pirovolakis, a four-year-old with the ultra-rare, neurodevelopmental condition SPG50 disease, earlier this year became the first person to be dosed with an experimental gene therapy developed to treat the disorder. The gene therapy was the result of a relentless pursuit by his parents, Terry and Georgia, to raise money and engage scientists and others in the development of a treatment for SPG50. We spoke to Michael’s father and founder of CureSPG50 Terry Pirovolakis and associate professor at UT Southwestern Medical Center Steven Gray, about SPG50, the work to develop and advance an experimental gene therapy for the condition into the clinic, and why Pirovolakis says his work is not yet done.

Matt Hay was a sophomore in college when he began to have problems with his hearing. He soon learned his hearing loss was caused by tumors on his nerves and was diagnosed with the rare condition neurofibromatosis. As a result of the condition, which can cause tumors to grow on nerves throughout the body, Hay has had to undergo 20 surgeries, including one to remove a tumor that blocked 80 percent of his spinal fluid and caused him to lose the ability to walk for a time. His diagnosis started him on not only a personal journey to fight his condition, but on a professional one as well as he became a patient advocate. We spoke to Hay, U.S. Director of advocacy for NF1 at Alexion, about his own journey as someone living with a rare disease, neurofibromatosis, and how his experience led him to become a patient advocate within the biopharmaceutical industry.

ENPP1 deficiency is a rare mineralization disorder that leads to calcification of soft tissue. About half of newborns with the condition will die in the first year of life, while others will live well into adulthood. The condition can cause hearing loss, arterial calcification, and complications involving the heart and brain. There are currently no approved therapies for ENPP1 deficiency. Inozyme is developing a therapy for ENPP1 deficiency and other rare mineralization disorders. We spoke to Axel Bolte, co-founder and CEO of Inozyme, about ENPP1 deficiency, its lead experimental therapy to treat the condition, and its work with Rady Children’s Institute for Genomic Medicine to improve the diagnosis of newborns with the disease.

Hereditary angioedema is a rare and potentially life-threatening genetic disease that causes sudden and prolonged swelling to various parts of the body. While there are therapies available today, they require either injection or infusions, carry inconvenient dosing regimens, and can cause undesirable side effects. Pharvaris is developing an oral therapy to treat HAE that it says could provide an effective and more convenient alternative to existing therapies. We spoke to Wim Souverijns, chief community engagement and commercial officer for Pharvaris, about hereditary angioedema, Pharvaris’ efforts to develop a convenient oral alternative to existing therapies, and why it believes it will be able to provide an effective alternative that is safe, tolerable, and convenient.

James Geraghty has had an up-close view of the rise of the rare disease drug industry as an entrepreneur, investor, and executive. Now he’s added the additional title of “author” with his new book “Inside the Orphan Drug Revolution.” Geraghty looks back through the past 40 years of his career starting with the passage of the Orphan Drug Act in 1983. We spoke to Geraghty about the catalysts that gave rise to the orphan drug industry, his concerns about the changing rare disease policy landscape, and why he believes it's essential for companies to take a patient-centric approach to drug development.

When Emily Rapp Black’s son Ronan was diagnosed with the rare and fatal condition Tay-Sachs disease, she turned to writing to make sense of her grief, what his short life would be, and what it meant to be his mother. Her memoir “The Still Point of the Turning World,” was written during Ronan’s life. Eight year’s later she wrote a companion memoir “Sanctuary” in which she explores learning to live after Ronan’s death, coming to terms with her loss, and learning that loss in not something that is overcome but rather absorbed into our beings. We spoke to Black about her two memoirs, her experience as a mother of a child with a rare and fatal disease, how she came to understand the meaning of resilience.

Alok Tayi thinks the biggest obstacle to treating patients with rare diseases isn’t finding potential treatments but funding them. Vibe Bio, a decentralized autonomous organization, is building a community of patient advocates and investors where holders of a crypto currency token Vibe sells each get to vote on how to invest its pool of money in rare disease drug development efforts. Once a decision is made to invest in the development of a therapy, Vibe creates a traditional corporation and uses conventional financing mechanisms. We spoke to Tayi, co-founder and CEO of Vibe Bio, about its approach, why he believes it will lead to the development of therapies that would otherwise go unfunded, and how the company’s decision-making model works.

X-linked adrenoleukodystrophy is a rare, inherited, neurodegenerative disease. It is a debilitating and chronic condition that is characterized by progressive weakness, stiffness, and muscle spasms, as well as sensory dysfunction, and incontinence. There is currently no approved treatment. Minoryx raised $51.4 million in May to support the application for marketing approval of its X-ALD therapy in Europe and to support launch preparations. We spoke Marc Martinell, co-founder and CEO of Minoryx, about X-ALD, the company’s experimental therapy leriglitizone, and why it’s being viewed as a potential treatment for other rare CNS diseases.

Oligonucleotide therapies can target the root cause of many diseases through the modulation of RNA expression and processing. Despite the promise of these medicines, their development has been limited by delivery challenges because they are not able to adequately reach heart and skeletal muscle, the critical affected tissues in neuromuscular diseases. PepGen is advancing next-generation oligonucleotide therapeutics that leverage its delivery platform technology to produce cell-penetrating peptide conjugates that improve the activity and tolerability of oligonucleotide therapies. We spoke to James McArthur, president and CEO of PepGen, about the company’s platform technology for conjugating peptides with oligonucleotides, how this allows it to target hard to reach tissue, and why it opens the potential for new therapies to treat neuromuscular and other diseases.

While biologics and gene therapies have altered what it means to have a rare disease for many people, one problem with these treatments is that they can trigger an immune response that can make a patient ineligible for gene therapies or render a medicine ineffective. Selecta Biosciences is developing a platform technology called ImmTOR that trains the immune system with precision not to react to specific antigens and can restore balance to the immune system. We spoke to Carsten Brunn, president and CEO of Selecta Biosciences, about the problem of immunogenicity to biologics, the company’s ImmTOR platform, and how its leveraging that platform with a growing pipeline of biologics and gene therapies.

Jenn McNary is a mother of children with rare conditions, as well as an outspoken advocate who has sought to elevate the patient voice in rare disease drug development. She was responsible for the organization of the largest FDA advisory committee hearing in history, with more than 1,000 Duchenne Muscular Dystrophy advocates, families, clinicians, and researchers in attendance. Now, as executive director and head of patient advocacy and engagement for Fulcrum Therapeutics, she’s working to inform company’s clinical trial designs through bringing in patients’ perspectives. We spoke to McNary about her journey as a patient advocate, her role as an advocate within industry, and how her views on the patient voice have evolved.

Clinical trials can get derailed for a variety of reasons that may have nothing to do with whether a drug works or not. Lokavant has developed an artificial intelligence platform that tracks disparate sources of clinical trials data in real time and through its predicative abilities alert companies to potential problems as they begin to emerge. The company said the system not only saves clinical trial sponsors time and money, but also improves the quality of outcomes. We spoke to Rohit Nambisan, CEO of Lokavant, about the company’s clinical trial data platform, how it works, and the role its system is playing in Ergomed’s Rare Disease Innovation Center.

Last year, the Retinal Degeneration Fund, a venture philanthropy established by the patient advocacy organization Foundation for Fighting Blindness, spun out Opus Genetics to develop gene therapies to treat rare, inherited, retinal diseases. The patient organization’s then CEO Ben Yerxa, who also headed the RD Fund, recently became the full-time CEO of Opus. We spoke to Yerxa about the genesis of Opus, its gene therapy pipeline, and what other patient organizations looking to take a more hands-on approach to therapeutic development can learn from its example.

African Americans are four times more likely than Whites to suffer from end-stage kidney disease. In part, that’s because of genetic causes underlying kidney-disease being more common in people of African descent. A recent study suggests that genetic testing and genetic counseling to patients of African ancestry changed behaviors and lowered their risk of developing kidney disease. We spoke to Maggie Westemeyer, a genetic counselor with the clinical genetic testing company Natera, about the genetic risks of kidney disease, racial health disparities, and how genetic testing can be used to address that and improve outcomes for patients.

The U.S. Food and Drug Administration’s Accelerated Approval pathway allows for the use of surrogate endpoints to make therapies more quickly available for unmet medical needs. About 82 percent of the drugs approved under the designation have been for orphan indications. But controversy around its use to win approval for Biogen’s Alzheimer’s disease drug Aduhelm last year set lawmakers off on an effort to reform how the pathway is used and to place new requirements on drugmakers. The healthcare consulting firm Vital Transformation recently did an analysis on the effects potential changes to the Accelerated Approval pathway could have and found that as many as two-thirds of treatments approved this way would no longer reach patients. We spoke to Duane Schulthess, CEO of Vital Transformation, about proposed reforms to the Accelerated Approval pathway, the findings of his firms’ analysis, and why these changes could have dire consequences for rare disease drug development.

Transthyretin amyloid cardiomyopathy, or ATTR-CM, is a progressive and potentially fatal heart disease. It is often overlooked because physicians tend to consider more common causes of heart failure. Black, African American, and Afro-Caribbean communities are at the greatest risk for the genetic condition, but also face greater barriers to accessing care. We spoke to Pfizer Vice President and North America Medical Lead Younos Abdulsattar and Pfizer Chief Medical Officer of Rare Disease Sonal Bhatia, about ATTR-CM; its disproportionate impact on the Black, African American, and Afro-Caribbean communities; and steps Pfizer is taking to work with community organizations to raise awareness and improve care for people with the condition.

In February, ProJenX launched to develop novel, brain-penetrant therapies that target defined pathways for the treatment of the rare neurodegenerative condition amyotrophic lateral sclerosis and other brain diseases. ProJenX lead candidate is prosetin, an experimental therapy developed through a collaboration between Project ALS and researchers at Columbia University. We spoke to Stan Abel, CEO of ProJenX, about ALS, the company’s lead therapeutic candidate prosetin, and the company’s ongoing relationship with Project ALS and Columbia University.

Dravet Syndrome is a severe genetic epilepsy characterized by lifelong seizures and neurodevelopmental impairment that starts in infancy. Camp4 is developing an RNA therapy that it believes can reduce the frequency and severity of seizures, or eliminate them, by upregulating a gene that underlies the condition. We spoke to Ann Barbier, chief medical officer of Camp4 Therapeutics, about Dravet syndrome, the company’s platform technology to develop therapies that can upregulate gene expression, and the potential to apply its approach to a broad range of conditions.

Plasmacytoid dendritic cells or pDCs are immune cells that help the body fight infections but in certain chronic autoimmune condition these cells can become continuously activated and cause the body to attack itself. Horizon Therapeutics is developing an experimental monoclonal antibody known as daxdilimab that can get certain immune cells to deplete the pDC and shut down chronic inflammation in these conditions. We spoke to Jodi Karnell, senior director of Research at Horizon Therapeutics, about the role of pDCs in certain autoimmune conditions, how daxdilimab works, and why it may offer a way to address a range of rare autoimmune condition for which there are no approved therapies or that are poorly addressed by existing treatment options.

As a scientist seeking funding to do rare disease research, Olivier Menzel confronted the lack of interest from funding sources. He eventually created the Blackswan Foundation to support research on any type of rare disease. Since then, the foundation has held scientific conferences, raised awareness about rare disease, and been involved in a large number of projects and collaborations around the world. The foundation also created the RE(ACT) Community, a crowdfunding and knowledge-sharing digital platform that connects researchers, patients, and other rare disease stakeholders. We spoke to Menzel, chairman and founder of the Blackswan Foundation, about the challenges of rare disease research, how it has worked to address common obstacles, and how it is serving as an accelerator to bridge the gap between basic scientific and commercial research.

Stoke Therapeutics platform technology allows it to target genetic diseases where people have one functional copy of a gene and one mutated copy. As a result, they can only produce half as much protein as they need to maintain health. Stoke seeks to restore missing proteins by increasing the protein output from healthy genes to compensate for the non-functioning copy of the gene. The company’s lead experimental therapy is an antisense oligonucleotide to treat the rare and progressive genetic epilepsy Dravet syndrome. We spoke to Ed Kaye, CEO of Stoke, about the company’s platform technology, how it works, and its lead program in Dravet syndrome.

After Alon Ben-Noon had a chance meeting with patient advocate Shay Rishoni, who suffered from the neurodegenerative condition ALS, he was so inspired by the experience that it led to his founding of NeuroSense Therapeutics to find a treatment for the condition. The company is pursuing synergistic combinations of existing therapies to go after biologic targets underlying the core pathologies of the disease. We spoke to Ben-Noon, CEO of NeuroSense, about the company’s approach to developing therapies, its current lead therapeutic candidate, and its efforts to target other neurodegenerative conditions beyond ALS.

The Russian invasion of Ukraine that began at the end of February has caused more than 5 million people to flee the country as the brutal assault has not spared civilian populations, schools, or hospitals. For people with rare diseases, the war has sent families in search of needed medications and care as they have crossed the border in search of help. Healthcare Education Institute, a Poland-base rare disease advocacy group, has been working to help Ukrainians with rare diseases get across the border, find accommodations, and connect them to medical care. We spoke to Adrian Goretzki, founder and president of the foundation, about the needs of Ukrainians with rare diseases, what his organization has been able to do to help, and why the humanitarian crisis for these rare disease patients will last beyond the current hostilities.

Genomics England is working to embed genomics into healthcare, enable research, and improve the diagnosis and treatment of patients. In 2018, it completed enrollment of its first initiative—the 100,000 Genomes Project—and is working on a new initiatives to explore the benefits and challenges of sequencing and analyzing the genomes of newborns. We spoke to Ellen Thomas, clinical director and director of quality for Genomics England, about the outcomes from the 100,000 Genomes Project, its Newborn Genomes Programme, and the potential for genome sequencing to alter the diagnostic odyssey for people with rare disease

Many people living with a rare and undiagnosed disease face a prolonged diagnostic odyssey that can be financially and emotionally taxing as they seek to put a name to what ails them. Co-founder and executive director of the Rare and Undiagnosed Network Gina Szajnuk and Co-founder and acting executive director of the Undiagnosed Diseases Network Foundation Cristina Might, both know what the search for a diagnosis is like and are working to help people find answers faster. Ahead of Undiagnosed Rare Disease Day April 29, we spoke to Szajnuk and Might about their own diagnostic odysseys, efforts to speed the path to a diagnosis, and the upcoming Undiagnosed Rare Disease Day.

One of the challenges of delivering enzyme replacement and other therapies to treat rare diseases is the questions of how to best deliver them. EryDel is developing therapies that can be encapsultated in a patient’s red blood cells through its proprietary, point-of-care device. We spoke to Luca Benatti, CEO of EryDel, about the company’s technology for encapsulating medicines in red blood cells, its pipeline of rare disease therapies, and the advantages delivering treatments this way.

Mary Mecham, a mother of two children with rare genetic disorders to whom she reads every day, grew frustrated by the lack of books that had characters who resembled her children. She began to search for stories that featured people with disabilities and met authors with disabilities who wrote about their own struggles. To share these works, she created Disability Book Week, which runs from April 23 to 29. We spoke to Brianna TenBrink, autism advocate and Disability Book Week panelist, about the portrayal of people with disabilities in literature, how that’s changing, and some good reads to consider for anyone interested in participating.

When Julia Vitarello learned that her daughter Mila had the CLN7 form of the deadly, neurodegenerative condition Batten disease, it set her off on a search for a treatment that resulted in the development of a customized antisense oligonucleotide. In the wake of Mila’s case, a movement has emerged to develop so-called N-of-1 therapies for people with ultra-rare conditions. Vitarello, along with Boston Children's Hospital researcher Timothy Yu, who developed the ASO to treat Mila, has co-founded the N=1 Collaborative, an international group seeking to enable the development of N-of-1 therapies to treat the thousands of patients in need. We spoke to Vitarello, CEO of Mila’s Miracle Foundation and co-founder of the N=1 Collaborative, about the new organization, the issues it is trying to address, and what it would take to take enable the development of individualized therapies broadly for patients with ultra-rare disease.

Recessive dystrophic epidermolysis bullosa is a rare, genetic, progressive condition caused by the deficiency of collagen type VII. People with severe cases of the condition suffer from blistering, vision loss, disfigurement, and other serious medical problems. Castle Creek Biosciences is developing a therapy that involves genetically modifying a patient’s own fibroblasts—the cells in the connective tissue—to get them to produce collagen VII. The modified cells are injected where needed and can be dosed repeatedly. We spoke to Matthew Gantz, president and CEO of Castle Creek, about the company’s experimental therapy for RDEB, how it works, and how the company is building out its pipeline through dealmaking.

Aristea Therapeutics was spun out of AstraZeneca to develop medicines for rare, immunologic disorders. Its lead program in development is an experimental therapy for a rare skin condition that causes repeated outbreaks of painful pustules on the hands and feet and is being looked at for other neutrophil-mediated diseases. We spoke to James Mackay, president and CEO of Aristea, about the decision to form the company, its lead therapy in development, and its collaboration and development deal with Arena Pharmaceuticals that gives its partner an option to acquire it outright.

RNA interference offers the potential disrupt the translation of instructions from genes with mutations into proteins that drive diseases. Silence Therapeutics is developing a pipeline of therapies based on its mRNAi Gold platform that allows it to target short interfering RNAs to liver cells. We spoke to Mark Rothera, who at the time served as CEO of Silence Therapeutics and Giles Campion, Silence’s chief medical officer and head of R&D, about the company’s platform technology, why it can be used to target a broad range of genetic diseases, and the company’s programs in development. Since recording this podcast, Rothera stepped down as CEO and the company named Craig Tooman, who had served as CFO of the company since January 2021, as its new president and CEO.

While advances have been made in the treatment of the rare blood cancer multiple myeloma, fundamental questions about how to optimize therapies for individual patients remain. The Multiple Myeloma Research Foundation launched CureCloud, an initiative to gather detailed genomic and health data from thousands of patients to both bring a precision medicine approach to the treatment of multiple myeloma and fuel the development of new breakthroughs. We spoke to Michael Andreini, president and CEO of the Multiple Myeloma Research Foundation, about the CureCloud initiative, the patient data it is gathering, and the potential to transform the treatment of multiple myeloma with precision medicine.

Carli Hamilton was diagnosed at age 2 with the degenerative neuromuscular disease spinal muscular atrophy. Though she wanted to be a mother once she got married, she feared passing the disease onto a child. She and her husband had genetic counseling to see if he was a carrier, but when her best friend became pregnant and told her that it was the hardest thing she had ever done and didn’t think Hamilton would be able to do it, she and her husband figured they would adopt. Nevertheless, Hamilton soon learned she was pregnant and today her daughter is 2. Hamilton, who has chronicled her pregnancy and motherhood on Instagram, discussed what pregnancy was like, how she handles the physical demands of motherhood, and what advice she would offer other SMA patients thinking of becoming pregnant.

The authors of four separate studies on the economic burden of rare diseases recently collaborated on piece in Health Affairs calling for concrete steps to address gaps in data that make it difficult to track rare diseases in the healthcare system. Though the authors came to similar conclusions in their reports, they were also stymied by existing data constraints, such as a lack of codes for rare diseases, differing data structures of electronic health records, and missed opportunities to gather data through public health surveys. We spoke to Joni Rutter, acting director of the National Center for Advancing Translational Sciences; and Annie Kennedy, chief of policy and advocacy for the Everylife Foundation for Rare Diseases, about the economic burden of rare diseases, the data constraints that limit a complete understanding of the impact they have, and what steps can be taken to improve the availability of patient data.

Rare Disease Week on Capitol Hill brings together rare disease community members from across the country to learn about federal legislative issues, meet other advocates, and share their stories with legislators. Because of ongoing concerns about the pandemic, this year’s event will be conducted virtually. We spoke to Britta Dornan, senior director of communications and marketing for the EveryLife Foundation and Sarah Tompkins, advocacy chair of Rare Disease Week on Capitol Hill 2022, about this year’s event, why rare disease patients should consider getting involved in legislative advocacy, and how rare disease patients and caregivers can best tell their stories to lawmakers.

One of the challenges various healthcare stakeholders face is making decisions based on limited and lagging data about the changing landscape. Komodo Health has collected a broad range of real-world data that allows it to capture a comprehensive view of patients moving through the healthcare system along with next-generation analytics to derive meaningful insights and drive decisions that improve patient outcomes. The company recently announced that it had entered into an agreement with the Chan Zuckerberg Initiative’s Rare As One network to provide software and analytic tools to help patient advocacy organizations in the network accelerate diagnoses, improve care, and advance research. We spoke to Web Sun, co-founder and president of Komodo Health, its platform technology, its potential to improve decision-making in the healthcare arena, and how members of CZI’s Rare As One network will be able to leverage its real-word data and analytic tools.

When Carly Flumer was 27 and working on her master’s degree in healthcare communication, she was diagnosed with thyroid cancer. Though she was successfully treated for the cancer, she now must live with the consequences of having had her thyroid removed, which requires lifelong care and treatment. The experience turned Flumer into a patient advocate as she has sought to share her story with others. We spoke to Flumer about her cancer journey, her experience in dealing with physicians who often spoke to her in terms she didn’t understand, and what she’d like other rare disease patients to learn from her experience.

Mammoth Biosciences is developing next-generation CRISPR products using alternatives to the Cas9 enzyme to read and write genetic code. The company, co-founded by Nobel laureate and CRISPR co-inventor Jennifer Doudna, is applying the technology broadly beyond therapeutics to include not only diagnostics, but agriculture, environmental monitoring, and biodefense. We spoke Trevor Martin, co-founder and CEO of Mammoth Biosciences, about the use of CRISPR as a diagnostic tool, the advantages alternatives to Cas9 may offer, and the company’s recently announced alliance with Vertex. Since recording this interview, Mammoth entered into a strategic collaboration with Bayer to use its CRISPR systems to develop in-vivo gene-editing therapies. That deal includes a $40 million upfront payment and more than $1 billion in potential milestones.

Antibody oligonucleotide conjugates are a new class of therapies that Avidity Biosciences is developing. These therapies combine the specificity of monoclonal antibodies with the precision of oligonucleotides. The company says by marrying these technologies together it is able to deliver RNA therapies to previously inaccessible tissue and cell types and more effectively target the underlying genetic drivers of diseases. The company is focused initially on muscle diseases but expects to expand out from there. We spoke to Sarah Boyce, CEO of Avidity Biosciences, about its antibody oligonucleotide conjugate platform, how its AOCs can deliver RNA therapies to tissue and cell types that were previously inaccessible, and it lead program in myotonic dystrophy type 1.

Illumina and the global nonprofit Genetic Alliance late last year unveiled the iHope Genetic Health program, which is aimed at providing whole-genome sequencing to patients across the globe impacted by genetic disease. At least half of iHope Genetic Health’s efforts will be focused on areas of the world in need outside the United States with more than one-third of Illumina’s support being dedicated to patients in Africa. Through the program, Illumina will enable Genetic Alliance to create networks of clinics, and laboratories equipped with the necessary genome technology to provide precision genomic diagnoses to patients suffering from rare genetic disease. We spoke to Ryan Taft, vice president of scientific research for Illumina, about the growing case for expanded use of genome sequencing as a diagnostic tool, the iHope Genetic Health program, and its efforts to expand use of the technology in low- and middle-income communities around the globe.

Primary biliary cholangitis is a rare, chronic, progressive, autoimmune disease of the liver. People with the condition suffer from inflammation, destruction of the intrahepatic bile ducts, and accumulate toxic bile acids that cause damage over time. The condition can lead to fibrosis, cirrhosis, and liver failure. CymaBay Therapeutics is developing an experimental therapy, Seladelpar, as a treatment for PBC. We spoke to Sujal Shah, president and CEO of CymaBay Therapeutics about PBC, Seladelpar, and why this first-in-class therapy has promise to address this condition with high unmet needs.

Most endocrinologists focus on the level of corticosteroids circulating in the bloodstream when treating conditions like the rare endocrine disorder Cushing syndrome. Sparrow Pharmaceuticals believes it is active intracellular steroids that are primarily responsible for causing toxicity in patients. It is developing therapies that target HSD-1, the key regulator of active intracellular steroids. We spoke to David Katz, founder and chief scientific officer of Sparrow Pharmaceuticals, about the company’s efforts to develop new approach to treating Cushing syndrome, how it works, and why this has the potential to address the unmet needs of patients with endogenous Cushing syndrome.

The advent of noninvasive prenatal testing allow for the use of a simple blood draw from a pregnant woman to tests fetal DNA for genetic conditions. As with liquid biopsies, these test rely on capturing cell-free DNA from the fetus circulating in the mother’s blood. We spoke to Paul Billings, chief medical officer for Natera, about the state of non-invasive prenatal testing, the growing use of these tests, and the range of conditions they can detect.

The growing concerns about equity, diversity, and inclusion has had particular resonance in the area of rare disease, where health disparities have been felt throughout the community. Eve Dryer, vice president of patient advocacy for Travere Therapeutics, has been involved in a number of efforts to address these issues and her company has played a critical role in funding initiatives to address health disparities that result from racial and socioeconomic drivers. On the heels of the recently completed Global Genes 2021 RARE Health Equity Summit, we spoke to Dryer about why Travere has focused on these issues, the work it is doing, and why it is such a critical issue for the rare disease community.

Many gene therapy companies seek to exploit a platform technology or leverage a specific vector. Rocket Pharmaceuticals is pursuing a multi-platform pipeline of treatments that directly target the genetic mutation underlying rare, childhood disorders. We spoke to Gaurav Shah, CEO of Rocket, about the companies approach to gene therapy, the conditions it’s targeting, and how it determines what gene therapies it will pursue.

When someone receives a diagnosis of a rare disease, they often find themselves in a strange land with no roadmap. The Tuberous Sclerosis Complex Alliance is helping patients with TSC better manage their condition with the TSC Navigator, an online tool intended to guide individuals and families through the complexities of TSC across their lifespans and live fuller lives. We spoke to TSC Alliance CEO Kari Rosbeck and TSC Alliance Director of Medical Affairs Ashley Pounders, about the TSC Navigator, the thinking behind it, and why it could serve as a model for other patient organizations to follow.

PI3K inhibitors have been an area of great interest for drug developers targeting cancers, but they’ve been difficult to turn into promising drugs due to safety concerns and a lack of efficacy in clinical trials. Pharming, though, believes PI3K can be a valuable target to treat APDS, a rare, immune condition. The company is working to develop Leniolisib, which it licensed from the drug giant Novartis in 2019. We spoke to Anurag Relan, chief medical officer of Pharming, about APDS, the role its PI3K inhibitors can play in treating the condition, and why these drugs may have broader use in autoimmune and inflammatory diseases.

While gene therapies hold great promise for patients with rare genetic diseases, one obstacle for ultra-rare conditions is that drug developer may view patient populations as being too small to make the development of a gene therapy economically viable. Taysha Gene Therapies, through its partnership with UT Southwestern, is rapidly developing a robust pipeline of gene therapies that leverage the same vector, manufacturing, and course of administration to enable the company to pursue indication that might not otherwise be feasible. The approach shows how rare disease patient advocates, academic researchers, and biotechnology companies can collaborate to enable treatments that would not otherwise be developed. We spoke to R.A. Session II, founder and CEO of Taysha Gene Therapies, about the origins of the company, its unique relationship with gene therapy innovator Steve Gray and UT Southwestern, and the critical role patient organization have played in the process.

Most people think of gene therapies as a way to replace a mutated gene with a copy that functions properly. But gene therapies are also being developed as a way to get the body to produce therapeutic proteins. AbbVie in September announced a strategic partnership with RegenxBio to develop and commercialize the company’s experimental gene therapy for wet age-related macular degeneration and other eye conditions. The one-time treatment, delivered to the eye, encodes for an antibody fragment designed to inhibit VEGF like the antibodies ophthalmologists regularly inject into the eyes of patients to treat the condition. We spoke to Ken Mills, CEO of RegenxBio, about wet-age macular degeneration, the company’s collaboration with AbbVie, and the potential to use gene therapy to alter the way patients with this and other eye conditions are treated.

While gene editing therapies promise to dramatically change the way that rare genetic diseases are treated, one challenge has been to find ways to deliver them directly into the body rather than first altering a patient’s cells in the lab and reinfusing them. iECURE is developing mutation agnostic in vivo gene editing therapies to address liver diseases. The company has exclusive licensing rights to three liver disorder programs from the University of Pennsylvania’s Gene Therapy Program and an option to license more than 10 additional candidates. We spoke to Joe Truitt, CEO of iECURE, about its in vivo gene editing therapies, its focus on liver diseases, and how it’s leveraging its partnership with Penn’s Gene Therapy Program.

Gene editing is an emerging therapeutic area that promises to correct the underlying genetic causes of diseases. Graphite Bio is readying to enroll its first patient in a phase 1/2 clinical study of its experimental gene editor GPH101 to correct the mutation in the beta-globin gene that drives sickle cell disease. Though the condition can manifest itself differently from patient to patient, it can cause painful episodes due to the clumping of sickle-shaped blood cells that obstruct blood flow in small blood vessels, as well as other acute complications including stroke and infections that can contribute to early mortality in these patients. We spoke to Josh Lehrer, CEO of Graphite Bio, about the company’s experimental sickle cell gene editing therapy, how it works, and what makes it a next-generation gene editor.

Homology Medicines is developing a range of genetic therapies based on a unique set of adeno-associated virus vectors derived from human hematopoietic stem cells that allow it to target a wide range of tissues. It is developing both gene therapies and gene editors simultaneously using these vectors. It’s lead program is an experimental gene therapy for phenylketonuria or PKU, a rare, genetic metabolic condition that causes an enzyme deficiency that results in an inability to breakdown the amino acid phenylalanine, which is common in protein containing foods. We spoke to Arthur Tzianabos, CEO of Homology Medicines, about the company’s genetic therapies, its program in PKU, and how it pairs its vectors and approach to meet the needs of a given condition.

Jon and Shirley Dicks’ daughter Elle first started developing problems swallowing when she turned 10 months old. As her difficulty eating progressed, she stopped growing. Her parents grew frustrated by doctors dismissing her symptoms until a passing comment that she seemed to have a sensitivity to light allowed a specialist to diagnose her with the rare, lysosomal storage disorder cystinosis. We spoke to the Dicks about Elle’s diagnostic odyssey, how having a diagnosis changed care for her, and the challenges they have faced caring for a child with a rare condition.

The ability to diagnose and treat rare diseases begins with data. The growing awareness about the need to collect data and do so in ways that are meaningful and usable to research and drug development communities, has mobilized a number of efforts to capture and make patient data available. AllStripes, formerly known as RDMD, completed a $50 million venture round in August to help it launch 100 new rare disease research programs. We spoke to Nancy Yu, co-founder and CEO of AllStripes, about the growing efforts around the collection of patient data, where AllStripes fits into this emerging landscape, and how data can transform the outlook for diagnosing and treating people with rare diseases.

While there is a steady stream of new gene therapies expected to be approved in the next decade, there are hundreds of diseases that could benefit from gene therapies but are not pursued by drug developers because they affect too small a population to be considered commercially viable. In an effort to change the economics of gene therapy for ultra-rare diseases, the Foundation for the National Institutes of Health is establishing the Bespoke Gene Therapy Consortium under its Accelerating Medicines Partnership program. The proposed five-year, $102.5 million program involves the National Institutes of Health’s National Center for Advancing Translational Sciences, the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research, and a group of commercial gene therapy developers. We spoke to P.J. Brooks, deputy director of the Office for Rare Diseases Research at NCATS and one of the architects of the program, about the need it is trying to address, why it is looking beyond translational science to issues including manufacturing and regulation, and how it hopes to accelerate the development of gene therapies for rare diseases. This episode is part of our ongoing Platforms of Hope series that explores advances in gene therapy and gene editing.

Despite the ability of whole genome sequencing to diagnose patients with rare genetic disease, the technology still leaves many patients without a clear diagnosis. Rady Children’s Institute for Genomic Medicine, which has innovated the use of rapid whole genome sequencing in the neonatal and pediatric ICU, is now working to diagnosed patients left undiagnosed by whole genome sequencing with long-read whole genome sequencing through a collaboration with Pacific Biosciences. We spoke to Matthew Bainbridge, principal investigator and associate director of clinical genomics at Rady Children’s Institute for Genomic Medicine, about the collaboration, how long-read sequencing differs from traditional whole genome sequencing, and why this is helping to find answers for undiagnosed patients with rare genetic diseases.

Many rare diseases cause unique changes to facial features that can provide insights for doctors seeking searching for a diagnosis. Researchers at Children’s National Hospital have developed software uses machine learning technology and images captured with a cellphone to quickly recognize disease patterns not immediately obvious to the human eye to help physicians accelerate the diagnosis of genetic syndromes by recommending further investigation or referral to a specialist in seconds. We spoke to Marius George Linguraru, who led the Children's National team that developed the digital biometric analysis software, about the diagnostic tool, how it works, and a deal with a newly formed company to commercialize the technology.

Advances in communication, information, and monitoring technologies have enabled the advent of decentralized clinical trials, but the COVID-19 pandemic crystalized the interest of regulators and trial sponsors. In fact, most biopharmaceutical companies today now expect to use elements of decentralized clinical trials in studies going forward. Science 37 is providing a software platform to enable decentralized clinical trials and offering a range of services on top of that to meet the needs of trails sponsors. We spoke to Jonathan Cotliar, chief medical officer of Science 37, about the move toward decentralized clinical trials, how technology is changing the types of data that can be gathered, and how it is forever reshaping clinical trials.

Chronic kidney diseases represent a growing worldwide problem with a lack of effective treatments. An improved understanding of the biology of kidney disease is fueling growing drug development activity. Chinook Therapeutics is focused on rare, severe chronic kidney diseases with well-defined clinical pathways. Its lead clinical program, atrasentan, is in a late-stage study in IgA nephropathy, a leading cause of chronic kidney disease. We spoke to Tom Frohlich, chief operating officer of Chinook, about rare kidney diseases, the company’s lead therapeutic candidate, and its plans for commercialization.

While genetic medicines promise to transform the way rare diseases are treated, one of the greatest challenges to realizing the full potential of these new therapies is the delivery of them to the cells within the body where they must go to be effective. James Dahlman, associate professor in the Department of Biomedical Engineering at Georgia Tech and Emory University, has been working to address this issue through the development of nanoparticles that could serve as vectors. We spoke to Dahlman about the delivery challenges of genetic medicines, how nanoparticles compare to viral vectors, and what it takes to develop new vectors that can deliver genetic medicines to where they need to go. This episode is part of our ongoing Platforms of Hope series that explores advances in gene therapy and gene editing.

RNA therapies offer great promise for addressing rare genetic diseases by disrupting the translation of pathogenic genes into disease-causing proteins or getting the body to produce a needed protein it lacks. But the challenge of delivering these therapies to tissue where they need to go to be effective has limited the diseases that have been treated with these therapies to date. DTx Pharma has developed platform technology to address the challenges of delivering RNA therapeutics and is building a pipeline of RNA therapies. We spoke Arthur Suckow, co-founder and CEO of DTx, about the delivery challenge of RNA therapies, how DTx’s platform technology addresses these, and how a $100 million financing from earlier this year will be used to fuel its growth.

When Genzyme won approval for an enzyme replacement therapy for Gaucher disease in 1991, the company launched a humanitarian aid program for rare diseases. Now as part of Sanofi, the pharmaceutical company has continued and expanded the program, which now includes five different lysosomal storage disorders, as well as rare blood disorders. We spoke to Bill Sibold, executive vice president of Sanofi Genzyme and president of Sanofi North America, about the company’s Humanitarian Aid Program, how it works; and how it overcomes the regulatory, infrastructure, and medical challenges of delivering these treatments to patients around the globe.

Ashley Walker spent the first 20 years of her life misdiagnosed as having a form of muscular dystrophy. It was only after her twin sons Alexander and Jayden suffered severe respiratory complications following their birth that she and her boys were all diagnosed with X-linked myotubular myopathy, a rare neuromuscular disease. Though the condition predominantly affects males, female carriers like Walker can also experience symptoms that can range from mild to debilitating, and even life-threatening. Her sons died eight years ago, a little more than a year after being born. Today, Walker is unable to work and requires breathing assistance at night, but she has become a patient advocate, and works to raise awareness about the disease known as XLMTM and the need for treatments. We spoke to Walker her own rare disease journey ahead of an externally-led XLMTM Patient-Focused Drug Development meeting, what life with XLMTM is like, and her hopes that new treatments are not far away.

The use of model system, such as fruit flies and worms, to screen existing drugs for their potential to treat rare genetic diseases offers a relatively fast and economic method to find candidates for repurposing. The success at screening 4,000 compounds in a worm model of the neurodegenerative disease ALS to identify a candidate that is now in human clinical testing gave rise to Modelis, a Canadian company that is now repeating the exercise in other rare diseases. We spoke to James Doyle, CEO of Modelis, about model system, how the company creates genetic avatars of patients; and how it works with rare disease drug developers, patient organizations, and patients to identify candidates for repurposing.

Charcot-Marie Tooth disease is a rare, genetic nerve condition that affects 150,000 Americans and nearly 3 million people around the world. Though the condition was first medically recognized in 1886, it is without an approved therapy. The CMT Research Foundation has been seeking to change that by addressing barriers to the development of therapies for CMT. We spoke to Susan Ruediger, founder and CEO of CMT Research Foundation, about its efforts to catalyze drug development for CMT, what it’s done to address obstacles, and some of the partnerships it has established to advance the development of treatments and potentially a cure.

DNA-modified cells can behave unpredictably in the body and there is a risk that they could proliferate uncontrolled, cause severe toxicities, and even survive unchecked for months or years. Cartesian uses its platform technology to engineer RNA into cells, making time-controlled changes. The company is developing treatments for cancer, respiratory conditions, and autoimmune diseases such as myasthenia gravis. We spoke to Murat Kalayoglu, president and CEO of Cartesian, about its RNA-engineered cell therapies, how they work and how the company is pushing the use of cell therapies beyond cancer.

Classic congenital adrenal hyperplasia, or CAH, is a potentially life-threatening rare genetic disorder characterized by an inability to produce the stress hormone cortisol while causing excess production of androgens, or male sex hormones. The condition has long-been treated with steroids, but about 70 percent of patients with the condition have poorly controlled disease. The problem is that it is difficult to give someone with CAH enough steroids to control the androgens without causing problems such as weight gain, increased blood sugar, and high cholesterol. As a result, doctors often underdose patients. Spruce Biosciences is developing an experimental therapy called tildacerfont, a non-steroidal therapy that binds to a receptor on the pituitary glands to limit the production of adrenal androgens and address that aspect of the disease. We spoke to Richard King, CEO of Spruce Biosciences, about CAH, how tildacerfont works, and what the company is doing to build a pipeline of other rare endocrine therapies behind it.

The imbalance between the supply and demand for gene therapy manufacturing capacity is creating opportunities for contract development and manufacturing organizations. Forge Biologics is seeking to leverage its expertise in AAV gene therapy as a CDMO while developing its own pipeline of experimental gene therapies. We spoke to Tim Miller, co-founder and CEO of Forge Biologics, about the company’s hybrid business model, how it hopes to differentiate itself through its shared experience with its customers, and its emerging pipeline of gene therapies to treat rare diseases.

Precision, safety, and durability are challenges for gene replacement and gene editing therapies. LogicBio Therapeutics says its GeneRide platform technology addresses these challenges by harnessing a natural DNA repair process. We spoke to Daniel Gruskin, chief medical officer of LogicBio, about the company’s platform technology, the advantages it provides, and the company’s lead experimental therapy for the rare metabolic condition methylmalonic acidemia.

Health records can be a rich source of data that can help provide an understanding of a rare disease and drive the development of therapies to treat them. But the siloing of this data, the use of inconsistent terminology, and the unstructured nature of aspects of these records all stand as barriers to harnessing their potential. The consumer health technology company Ciitizen is working to give patients greater control over their own health data and enable its sharing with researchers and providers. We spoke to Nasha Fitter, vice president of rare disease for Ciitizen, about her own experience as a mother of a child with a rare neurologic condition, her work as a rare disease advocate, and a collaboration between a group of rare neurologic disease advocacy organizations to build a natural history study on the Ciitizen platform.

The translational challenges of moving an experimental therapy from the lab to the clinic can stall the development of life-saving therapies, but Passage Bio has provided a unique solution to that challenge. The company’s strategic collaboration and licensing agreement with the University of Pennsylvania’s Gene Therapy Program leaves the discovery and preclinical work in the hands of Penn researchers and provides it with enhanced access to a broad portfolio of gene therapy candidates and future innovations. The company has built a pipeline of gene therapy candidates targeted central nervous system disorders. We spoke to Bruce Goldsmith, CEO of Passage Bio, about the company’s relationship with Penn’s Gene Therapy Program, its focus on CNS conditions, and the company’s lead program in the rare lysosomal storage disorder GM1 gangliosidosis.

Earlier the month the U.S. Food and Drug Administration approved Apellis Pharmaceuticals Empaveli to treat paroxysmal nocturnal hemoglobinuria (PNH), a rare and life-threatening condition in which the body’s immune system destroys the oxygen carrying red blood cells. Like existing treatments Soliris and Ultomiris, Empaveli works to inhibit the complement system, but it is the first therapy to target the portion of this immune cascade known as C3. We spoke to Cedric Francois, co-founder and CEO of Apellis, about Empaveli, what advantages it may provide over existing therapies for PNH, and other indications the company will pursue for this medicine.

In some diseases, such as lysosomal storage disorders, proteins are unable to serve their normal functions because they become misfolded. While some approaches, such as enzyme replacement therapies, have been used to treat these conditions, they can have significant limitations. Gain Therapeutics has developed a platform for using small molecule therapies to return proteins to their proper shape and restore their function. We spoke to Eric Richman, CEO of Gain Therapeutics, about its platform technology, how it works, and why it offers a compelling alternative to other approaches to treating lysosomal storage disorders.

Mouse models can play an essential role in allowing researchers to understand rare diseases and develop drugs to treat them. Cat Lutz, senior director of mouse repository and in vivo pharmacology genetic resource science at The Jackson Laboratory, researches mice as a model for human neurodegenerative disease. The lab’s mouse repository and Rare and Orphan Disease Center today features more than 12,000 unique strains including more than 1,700 live colonies that are distributed to the scientific community. We spoke to Lutz about the role mouse models play in rare disease research, how new gene editing technologies are changing the development of mouse models, and why new technologies are unlikely to displace their use anytime soon.

The recruitment of patients for rare disease clinical trials can be challenging because of issues such as small patient populations and their geographic dispersity, but the failure to take a patient-centric approach in designing trial protocols can add to the difficulties sponsors face in conducting such studies. The Center for Rare Diseases at PRA Health Sciences recently issued a toolkit focused on patient-centric trial development for sponsors, participants, and advocates. We spoke to Scott Schliebner, senior vice president and head of the Center for Rare Diseases, about designing patient-centric clinical trials, why it matters, and what sponsors can do to stay focused on patients.

The advent of genome editing is creating the potential to correct the underpinnings of genetic diseases by rewriting the mutations that cause them. Before these emerging technologies can be put to use to treat and cure genetic diseases broadly, a number of challenges must be overcome. These include such things as validating new gene editing technologies, finding ways to deliver them precisely to the right cells and tissues in the body, and developing means to detect off-target effects. The National Institutes of Health created the Somatic Cell Genome Editing program to address broad challenges of gene editing with the goal of accelerating the development of new therapies for a wide range of condition through the creation of a toolkit that could be made available to biomedical researchers. We spoke to Erik Sontheimer, co-chair of the Somatic Cell Genome Editing Consortium's steering committee, about the program, the challenges it is seeking to address, and it potential to accelerate the development of a new generation of genetic medicines. Thanks to Pfizer, Inc., Bluebird, and Novartis Gene Therapies for their support of this podcast, part of our Platforms of Hope: Advances in Gene Therapy and Gene Editing series.

PTC Therapeutics, through its partnership with the SMA Foundation and Genentech, won approval last year for Evrysdi, the first oral therapy for the rare neurodegenerative condition spinal muscular atrophy. Now, the SMA Foundation is working with the company to discover and develop regenerative treatments that can reverse the damage done by the disease. At the same time, the company is advancing its effort on the gene therapy front following its 2018 acquisition of Agilis Biotherapeutics. We spoke to Matthew Klein, chief development officer for PTC Therapeutics, about the company’s work in SMA, its move into regenerative medicine, and its efforts to win approval in Europe and the United States for its first gene therapy.

Chandler Crews was born with the rare, genetic condition achondroplasia, the most common form of dwarfism. In 2010, she decided to undergo a series of limb lengthening surgeries, which over a four-year period increased her height to 4’ 11” from 3’ 10.” We spoke to Crews, founder and president of the nonprofit patient organization The Chandler Project, about her experiences living with the condition, her decision to undergo the surgery, and how she views new therapies working their way through clinical development that seek to promote growth in people with achondroplasia.

Children’s Mercy Research Institute has been expanding its efforts to understand the genetics underlying rare diseases. Earlier this year, it opened a new home in downtown Kansas City and at the end of last year launched Genomic Answers for Kids, a first of its kind pediatric data repository and the institutes flagship research initiative. We spoke to Tom Curran, senior vice president, chief scientific officer, and executive director of the Children’s Mercy Research Institute, about the program, its ambitious efforts, and it focus on translational research.

Gene therapy is promising to provide treatments and potential cures for a long list of rare, genetic diseases. A key element of these therapies are the viral vectors that are used to deliver and insert the genetic material used to treat a patient. Guangping Gao, co-director of the Li Weibo Institute for Rare Diseases Research, director of the Horae Gene Therapy Center and Viral Vector Core, and professor at the University of Massachusetts Medical School; and Phillip Tai, assistant professor at the University of Massachusetts Medical School, discuss a recent review article that they co-authored in Nature’s journal Signal Transduction and Targeted Therapy that looks at viral vector platforms for gene therapy. We spoke to the researchers about viral vectors, the role they play in gene therapy, and the decision process that goes into the selection of a vector of a specific gene therapy. Thanks to Pfizer, Inc., Bluebird, and Novartis Gene Therapies for their support of this podcast, part of our Platforms of Hope: Advances in Gene Therapy and Gene Editing series.

Sanath Kumar Ramesh’s son Raghav was born with an ultra-rare and progressive disorder known as SSMD. The condition is caused by mutations in the GPX4 gene. There are only a handful of known patients with GPX4 mutations. In the past, most known cases resulted in death about a month after birth. Ramesh has moved with remarkable speed to find patients, raise money, and drive research. But he also realized that many other parents of children and small, rare disease organizations must go through the same process to develop treatments for ultra-rare conditions. To guide and accelerate the work for others, Ramesh has created OpenTreatments Foundation, a nonprofit with the with a software platform to enable treatments for genetic diseases regardless of rarity or geography. OpenTreatments provides people with a road map for developing genetic medicines; connects them with researchers, clinicians and other needed to advance their programs; and helps them show their capabilities to raise funding despite the rarity of a condition. We spoke to Ramesh, founder of OpenTreatments Foundation, about how his software platform works, the need it addresses, and how it can accelerate the development of treatments for ultra-rare genetic diseases.

In his new book, Emmy-winning news and documentary television producer Miguel Sancho recounts the efforts he and his wife Felicia Morton went through to get their son Sebastian diagnosed and treated for chronic granulomatous disease, a rare and deadly immunodeficiency. The book “More than You Can Handle: A Rare Disease, a Family in Crisis, and the Cutting-Edge Medicine that Cured the Incurable” follows some familiar territory for books in the genre but diverges in its willingness to explore the strains on a marriage that can arise when a child becomes ill with a rare and deadly disease, the difficulties parents can have coping, and the post-traumatic stress disorder that can follow even a successful cure. We spoke to Sancho and Morton about their journey to get their son diagnosed and treated, the challenges they faced, and how, after a period of relying on the generosity of others, they found healing in turning their attention outward to help others.

The Innovative Genomics Institute; a partnership between the University of California, Berkeley and the University of California, San Francisco led by Nobel laureate Jennifer Doudna; is working to harness CRISPR-based genome editing to correct underlying mutations in monogenic diseases. The institute is initially focusing its efforts on sickle cell disease and a rare familial autoimmune disorder. We spoke to Fyodor Urnov, director of technology and translation at the Innovative Genomics Institute, about its efforts to advance genome editing technology, its work on sickle cell disease; and why it is critical for researchers to consider issues like access, affordability, and scalability in developing genetic medicines. This episode is part of our ongoing Platforms of Hope series. Thanks to Pfizer, Inc., Bluebird, and Novartis Gene Therapies for their support of this podcast, part of our Platforms of Hope: Advances in Gene Therapy and Gene Editing series.

The economic burden of rare disease in the United States reached nearly $1 trillion in 2019, according to a new study from the Everylife Foundation for Rare Diseases. About 43 percent of that total is for direct medical costs. The balance includes such things as forced retirement, absenteeism, and presenteeism—the lost productivity of people who show up to work but are not fully functioning. We spoke to Annie Kennedy, chief of policy and advocacy at the EveryLife Foundation, about the study, its policy implications, and why the numbers are conservative.

The ability to target the underlying cause of a disease and make a lasting correction makes gene therapy an attractive approach to treating neurodegenerative conditions. The advent of Zolgensma, a gene therapy for the treatment of the rare neurodegenerative condition spinal muscular atrophy, serves as a model for this approach. A recent review article in Nature Neuroscience looks at the advances in development of gene therapies for neurodegenerative disease and considers the challenges and promises. We spoke to article co-author Subhojit Roy, professor in the departments of Pathology and Neuroscience at the University of California, San Diego, about the pace of activity in this area, why he believes it is so promising, and its potential extend beyond monogenic diseases. This podcast is part of our ongoing Platforms of Hope series that explore advances in gene Thanks to Pfizer, Inc., Bluebird, and Novartis Gene Therapies for their support of this podcast article, part of our Platforms of Hope: Advances in Gene Therapy and Gene Editing series.therapy and gene editing. Thanks to Pfizer, Inc., Bluebird, and Novartis Gene Therapies for their support of this podcast, part of our Platforms of Hope: Advances in Gene Therapy and Gene Editing series.

Poseida Therapeutics is perhaps best known for its immune-oncology cell therapy products, but the company’s platform technologies are also being used to develop a growing pipeline of gene therapy candidates. While the most advanced ones in its pipeline use viral vectors, newer candidates make use of a non-viral nanoparticle vector. This technology can increase the payload of the gene therapy, avoid issues of immunogenicity, allow for redosing, and deliver manufacturing advantages. We spoke to Eric Ostertag, CEO of Poseida, about the company’s platform technology, its gene therapy pipeline, and its efforts to move beyond viral vectors. Thanks toPfizer, Inc.,Bluebird, andNovartis Gene Therapiesfor their support of this podcast, part of ourPlatforms of Hope: Advances in Gene Therapy and Gene Editingseries.

Jazz Pharmaceuticals has been successful at building and commercializing a growing pipeline of therapies to treat rare neurologic conditions and hematologic cancers. Central to its strategy has been the use of acquisitions to build its pipeline. In fact, we should note that since recording this podcast, the company continued that approach with news that it would acquire GW Pharmaceuticals for $7.2 billion to expand its neuroscience portfolio. We spoke to Robert Iannone, executive vice president of research and development and chief medical officer of Jazz about the company’s neuroscience pipeline, its growing family of commercial products, and how its preparing to maintain its leadership in the treatment of the rare sleep disorder narcolepsy as new competitors move toward market.

CRISPR is a powerful editing tool, but it works best as a way to knock out genes rather than correct them. New approaches to gene editing, though, are providing the promise of more effective tools for addressing the underlying drivers of monogenic diseases. A recent study in Nature of an approach known as base editing in a mouse model of the ultra-rare genetic condition progeria, a disease that causes premature aging, demonstrated the powerful potential of the approach. While CRISPR has been likened to scissors, base editing has been compared to the find-and-replace function of a word processor. We spoke to study leader David Liu, director of the Merkin Institute for Transformative Technologies at the Broad Institute, about base editing, how it works, and why it may offer the potential to treat a wide range of rare diseases. This episode is part of an occasional series on innovations in gene editing and gene therapy.

Arya Singh grew up with a child’s-eye-view of hospitals, operating rooms, and clinical trial sites. As someone with the rare and progressive neuromuscular disorder spinal muscular atrophy type 2, Singh knew what it meant to be isolated and frightened by both as a patient and a clinical trial participant. Now a student at Yale University with plans to pursue her interests in law and public policy in health, she has written Courageous Calla and the Clinical Trial. We spoke to Singh about the surgeries and clinical trials she endured as a child, her new book Courageous Calla, and her interest in humanizing medicine.

Glioblastoma is an aggressive and rare brain cancer. Though it is typically treated with surgery, radiation, and chemotherapy, the prognosis for patients is grim with only 10 percent of surviving at least five years. Plus Therapeutics is developing a pipeline of radiotherapies that are encapsulated in nanoliposomes. Through novel deliver and formulation of these therapies, the company believes it can produce safer and more efficacious treatments. We spoke to Marc Hedrick, CEO of Plus Therapeutics, about the company’s nanoliposome technology, how it works, and why the company is focusing on rare cancers.

Patients’ data is critical to rare disease innovation, but it does little to help advance progress if it is not widely accessible to researcher. RARE-X is a nonprofit working to bust data silos through a federated data-sharing platform and empower rare disease patient communities to more easily gather, structure and securely share critical data through a common platform. We spoke to Nicole Boice, co-founder and executive director of RARE-X, about the problem RARE-X is seeking to address, the technology and expertise the organization has been able to bring together, and why data sharing is essential to accelerating the diagnosis or rare diseases and development of new treatments to treat them.

The genetic basis of sickle cell disease has been long understood, but it has only been recent that new treatments and a growing pipeline of therapies have emerged. The inherited blood disorder causes red blood cells to become crescent shaped, which restricts the flow in blood vessels and limits oxygen delivery to the body’s tissues leading to severe pain and organ damage. At the end of 2019, Global Blood Therapeutics won accelerated approval for Oxbryta, the first FDA-approved therapy that directly inhibits sickle hemoglobin polymerization, the root cause of sickle cell disease. We spoke to Ted Love, president and CEO of Global Blood Therapeutics, about the changing landscape of sickle cell disease, Oxbryta and the company’s pipeline behind it, and how the company is approaching the global need for the drug given the higher prevalence of the disease in parts of the world.

At the end of November, the U.S. Food and Drug Administration approved Rhythm Pharmaceuticals Imcivree, the first therapy for chronic weight management in patients with certain genetic forms of obesity. The approval validates Rhythm’s approach to target a specific biological pathway common to a number of these conditions. We spoke David Meeker, CEO of Rhythm, about genetic obesities, the company’s drug Imcivree, and his plans to expand its use beyond the initial approved indications.

Orchard Therapeutics founder and former chief scientific officer Bobby Gaspar took the helm of the gene therapy company in March to replace CEO Mark Rothera when he stepped down. Since taking over, Gaspar has led a restructuring of the company and narrowed the focus to prioritize what it saw as high-value programs including its gene therapy for metachromatic leukodystrophy, a rare and life-threatening inherited disease of the body’s metabolic system. We spoke to Gaspar about the company’s sharpened focus, its gene therapy in development for metachromatic leukodystrophy, and where he sees the greatest opportunities for Orchard going forward.

Tessera Therapeutics is seeking to move beyond gene editing and gene therapy to what it calls “gene writing.” The company said its technology can be used to change base pairs, make small insertions or deletions, and integrate entire genes into the genome. We spoke to Geoffrey von Maltzahn, co-founder and CEO of Tessera, about the company’s gene writing technology, how it works, and the potential for it to accelerate the pace of genetic medicine.

In November, the U.S Food and Drug Administration approved Eiger Biopharmaceutical’s Zokinvy, the first therapy to treat the ultra-rare disorder progeria, a genetic disease that causes premature aging. The approval of Zokinvy, which began life as a potential cancer therapy known as lonafarnib, shows the essential role patient organization can play in driving research and bringing together collaborators to advance the understanding of a condition and develop treatments. We spoke to Leslie Gordon, co-founder and medical director of the Progeria Research Foundation, about the role the organization has played in creating an understanding of progeria, identifying and advancing a therapy for the condition, and how a windfall from the sale of a priority review voucher from the approval of the therapy will help advance future research.

The rare disease drug developer Retrophin has been through a number of changes in recent years including a new CEO, a late-stage failure of a key program, and the resolution of dueling lawsuits between it and its former CEO and convicted fraudster Martin Shkreli. Now with data from its lead experimental therapy sparsentan expected next year in two different rare kidney diseases, the company has changed its name to Travere Therapeutics. We spoke to Eric Dube, CEO of Travere, about the company’s new identity, its experimental therapy sparsentan, and the rare kidney diseases it is being developed to treat.

While gene therapies provide great promise for people with rare, genetic diseases, the pursuit of these one-time treatments may not seem economically viable to commercial developers. In the case of ultra-rare conditions, the patient populations may be so small that it may not be possible for companies to recoup their investments, let alone make a profit. The nonprofit Columbus Children’s Foundation is providing funding and scientific resources to accelerate access to gene therapies for children with ultra-rare genetic disorders. We spoke to Jude Samulski, a gene therapy innovator and chairman and chief scientific officer of the Columbus Children’s Foundation, about the foundation operates, the range of capabilities it is able to bring together, and the potential to scale what it does to reach more patients in need of treatments.

Daniel de Boer became a biotech executive after his son was diagnosed with the genetic respiratory disease cystic fibrosis. He founded ProQR Therapeutics with an initial focus on developing RNA therapies to treat cystic fibrosis, but the company has since turned its attention to a group of rare, inherited retinal diseases that cause blindness. We spoke to de Boer, CEO of ProQR, about the evolution of ProQR, its pipeline of antisense oligonucleotide therapies, and the advantage of this approach in treating rare eye diseases.

The economics of developing gene therapies can make it unattractive for biopharmaceutical companies to invest in bringing a gene therapy through development and to the market for ultra-rare conditions. But researchers at the National Center for Advancing Translational Sciences are working to develop a set of gene therapy vectors that can be used in multiple indications and eliminate the time and cost of preclinical development for a range of conditions through its Platform Vector Gene Therapy, or PaVe-GT program. In this fourth and final part of our gene therapy series, we spoke to P.J. Brooks, program director in the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences, about the PaVe-GT program, the potential for developing a toolkit of plug-and-play vectors, and how this can alter the cost of developing gene therapies for ultra-rare and individual patients. This series is made possible through support from BioMarin, Pfizer, Retrophin, Novartis Gene Therapies (formerly AveXis), UCB Inc., Genentech, Ultragenyx, Novartis, RegenxBIO, and Sangamo Therapeutics.

Though there are only a handful of gene therapies on the market today, there is a robust and growing pipeline of these transformative medicines advancing toward market. In this third part of our gene therapy series we spoke to Janet Lambert, CEO of the Alliance for Regenerative Medicine, about the state of the gene therapy industry, the challenges developers face in advancing therapies to the market, and emerging pricing approaches to make them accessible to the patients who need them. This series is made possible through support from BioMarin, Pfizer, Retrophin, Novartis Gene Therapies (formerly AveXis), UCB Inc., Genentech, Ultragenyx, Novartis, RegenxBIO, and Sangamo Therapeutics.

Shortly after birth, Kim Nye’s first daughter Tessa began suffering seizures. Though Nye gave birth to other children without significant health issues, when her fourth child Colton was born, he had the same symptoms as his oldest sister. The two siblings were eventually diagnosed with an ultra-rare genetic disorder and Nye began the TESS Research Foundation. The organization has been pursuing a gene therapy, which a biopharmaceutical company is now working to develop. In this second part of our series on gene therapies, we spoke to Nye about her own journey to becoming a rare disease advocate, how a gene therapy fit into her organization’s research agenda, and the considerations she is weighing before dosing her children with an experimental gene therapy.

Genetic counselors play a unique role in the medical life of a person with a rare disease. They can serve as guide, translator, and trusted advisor. In this first part of our four part series on gene therapies, we spoke to genetic counselor Stephanie Gandomi, a Global Genes advocacy resource, about gene therapies, the role genetic counselors play in working with rare disease patients, and the considerations rare disease patients may make about whether to pursue a gene therapy through a clinical trial.

This series is made possible through support from BioMarin, Pfizer, Retrophin, Novartis Gene Therapies (formerly AveXis), UCB Inc., Genentech, Ultragenyx, Novartis, RegenxBIO, and Sangamo Therapeutics.

Nell Meosky Luo remembers the way her mother use to keep extensive journals documenting the symptoms and treatments of her brother, who has a rare immune disorder. It served as inspiration for Folia Health, which has developed a platform that allows patients and caregivers to maintain health records, manage their conditions, and communicate with their physicians. We spoke to Luo, founder and CEO of Folia Health, about how patients are using the platform, its potential to gather real-world data, and how the data it gathers could be used to advance the understanding of rare diseases.

Kezar Life Sciences is developing therapies for immune-mediated disorders and cancer. It’s lead experimental therapy is in development for the rare autoimmune condition lupus nephritis. It is a first-in-class therapy that targets master regulators of cellular function. We spoke to Noreen Henig, chief medical officer for Kezar, about lupus nephritis, the company first-in-class candidate to target the condition, and why it may have application in a broad range of autoimmune diseases.

In 2006, at the age of 29, Ben Munoz suffered a stroke from a rare condition known as arteriovenous malformation. One of the things that were critical in his treatment and recovery was the connection he was able to make with another person who had the same condition and had experienced what Munoz was going through. Munoz co-founded the nonprofit Ben’s Friends, which operates an expanding set of patient communities for people with specific rare conditions to connect and support each other. We spoke to Munoz, about his own experience with a rare condition, the role support from someone with his own condition has played, and his efforts to create a forum where patients with specific conditions can connect and provide support to each other.

It began as a Facebook post for someone looking for help getting a child with a rare neurological condition whole genome sequencing. It resulted, though, in groundbreaking work by Timothy Yu, a neurologist and attending physician in the Division of Genetics and Genomics at Boston Children’s Hospital to develop a custom antisense oligonucleotide therapy for the little girl, who had a rare form of the neurodegenerative condition Batten disease. The work to design and deliver an antisense therapy in under a year has excited the rare disease community for the potential of individualized therapy that address the underlying genetic mechanisms of rare diseases. We spoke to Yu about his work, the potential to industrialize the creation and delivery of individualized therapies for rare disease patients, and the challenges that need to be addressed.

Clinton Moore was a reluctant rare disease advocate. It took several years for him to become engaged in the rare disease community after his son Chandler was diagnosed with cystinosis, a rare, genetic, metabolic disease. Moore, who today is president of the Cystinosis Research Network, can add filmmaker to his credits. Moore tells his son’s story in a full-length documentary Walk in My Shoes. The film, which is available for free on YouTube, offers a view into the daily life of a boy and his family dealing with a rare disease. We spoke to Moore about his son’s rare disease journey, his own emergence as an advocate, and how he came to recognize the power of an individual to make a difference.

Venous and lymphatic malformations are types of congenital vascular anomalies that are present at birth. These malformations can cause a number of complications including pain, bleeding, and impairment of the affected area. Current treatments options are limited and there are no drugs approved for these conditions. Venthera, a BridgeBio affiliate, is developing a topical gel for the treatment of venous and lymphatic malformations that targets signaling pathways that drive them. We spoke to Thom Rossi, CEO of Venthera, about the company’s lead experimental therapy, its first-in-man-trial, and how it is leveraging the resources of BridgeBio.

Niemann-Pick disease is a rare and often-fatal genetic, metabolic disorder with no approved treatments, but that could soon change as new therapies advance through the development and approval process. In anticipation of the first therapies for the disorder becoming available, the National Niemann-Pick Disease Foundation has been working to prepare patients and their families for new obstacles they may need to navigate to obtain access and reimbursement for these treatments. We spoke to Joslyn Crowe, executive director of the National Niemann-Pick Disease Foundation, about what her organization is doing to prepare the community for the availability of the first therapies for the conditions, the issues people will need to consider, and how families may need to think differently about their futures.

Cara O’Neill was a practicing pediatrician, but after her daughter was diagnosed at age 3 with Sanfilippo syndrome, she turned her attention to driving research into the rare lysosomal storage disorder. Today, O’Neill serves as the chief science officer of Cure Sanfilippo Foundation, an organization she and her husband founded. It has since funded $6.5 million in research through more than 20 scientific projects and clinical trials. We spoke to O’Neill about Sanfilippo syndrome, her journey from physician to advocate, and her efforts to craft a research agenda.

Chiasma is developing oral formulations of injectable drugs using its proprietary drug development technology. This allows therapies that would normally break down in the stomach to reach the small intestine, where they can be absorbed. At the end of June, the company won approval for Mycapssa, the first and only oral therapy to treat acromegaly, a rare condition in which the overproduction of growth hormone can lead to serious health conditions. It was the first drug approved using the company’s drug delivery technology. We spoke to Raj Kannan, CEO of Chiasma, about the company’s recently approved therapy for acromegaly, the company’s drug delivery technology, and the value of having oral alternatives to injectable therapies.

The world of health insurance can appear complex and confusing. For young adults with rare and chronic conditions, navigating their coverage options for the first time may also require them to consider access to specific physicians, services, and therapies. We spoke to Colleen Huysman, a clinical social worker with the Bridges Adult Transition Program at Boston Children’s Hospital, and Sneha Dave founder and executive director of the Health Advocacy Summit, about the issues young adults with rare and chronic condition need to think about as they seek health coverage, the types of choices they will face, and how to best go about navigating this dense and opaque world. As a note, look for more topics like this at this year’s Global Genes Live event and going forward as the organization moves to increase educational efforts around managing the financial challenges of living with a rare disease.

The debate over pricing of therapies often centers on the question of value and how to best determine it. The consulting firm Charles River Associates took an interesting approach to understanding the way payers view the pricing of rare therapies. Instead of asking them about pricing in terms of value, they asked about it in terms of fairness. We spoke to Andrew Parece and Matthew Majewski, both vice presidents with Charles River Associates, about how payers view the pricing of rare disease therapies, how context changes perceptions around pricing, and why they began questioning payers about the issue of fairness.

Narcolepsy is a rare neurological sleep disorder with limited treatment options. Avadel is working on a controlled-release formulation of the standard of care, sodium oxybate, that allows for a once nightly dose of the drug. We spoke to Greg Divis, CEO of Avadel, about the company’s experimental therapy for narcolepsy, how it improves on the existing standard of care, and how it breaks with the company’s existing base of business. Editor's note: We recorded this podcast in late June. During the interview, Divis discussed the company's hospital products. On July 1, 2020, Avadel announced the sale of its hospital products portfolio to strategically focus on advancing FT218 through the FDA regulatory review process.

Idiopathic pulmonary fibrosis is a family of lung diseases characterized by scarring and thickening of lung tissue leading to an irreversible loss of lung function and reduced life expectancy. In normal times, the dry and persistent cough the condition can cause, can have a big impact on a person’s quality of life, but in the midst of a pandemic where coughing is a sign of infection, it can be particularly isolating. Respivant Sciences is developing an experimental therapy that treats IPF patients who suffer from a persistent cough. We spoke to Bill Gerhart, CEO of Respivant, about IPF, what life with the condition can be like, and the company’s experimental therapy to treat the it.

Ionis Pharmaceuticals has been a pioneer of antisense therapies, which target RNA to either disrupt production of a disease-causing protein or upregulate needed proteins in people who are deficient. The company is in late stage development of a promising therapy to treat Huntington’s disease, a rare and fatal neurodegenerative condition. But the company is also working on advancing a new generation of antisense therapies to improve the safety and efficacy of these treatments. We spoke to Eric Swayze, executive vice president of research for Ionis, about its experimental Huntington’s disease therapy, its efforts to treat the condition, and what the next generation of antisense therapies will look like.

Short Bowel Syndrome is a life-threatening rare disease caused by a significant shortening of the gastrointestinal tract. Because of difficulties people with short bowel syndrome have properly absorbing nutrients they rely on receiving them through intravenous infusions. This has an impact on the quality of life of people with the condition and comes with a high risk of systemic infections. 9 Meters Biopharma is focused on rare gastrointestinal conditions. It is advancing an experimental therapy for short bowel syndrome. We spoke to John Temperato, president and CEO of 9 Meters Biophama, about short bowel syndrome, the company’s experimental therapy to treat the condition, and how the company has built its pipeline through two recent mergers.

Huntington’s disease is a rare and fatal neurodegenerative condition that is without any disease-modifying therapies today. Vaccinex is developing an experimental therapy designed to treat Huntington’s disease by addressing neuroinflammation, a hallmark of the condition that it shares with other neurodegenerative diseases. We spoke to Maurice Zauderer, president and CEO of Vaccinex, about the role of neuroinflammation plays in Huntington’s disease, its experimental therapy to treat the condition, and why it may provide benefits to people with other neurodegenerative diseases.

When Sandra Bedrosian Sermone grew frustrated by the slow pace of a drug developer working to advance a potential therapy for ANDP, a rare condition her son has, she and another parent of a child with neurodevelopmental disorder began to search for a potential drug to repurpose. Their work suggested low doses of the powerful anesthetic ketamine could up regulate activity of the ADNP gene and provide benefit to patients. Now, a clinical trial of low-dose ketamine is getting underway thanks to their efforts. We spoke to Bedrosian-Sermone, founder and president of the ADNP Kids Research Foundation, about ADNP, her efforts to find a potential treatment for it, and how a patient advocate without formal science training can alter the therapeutic landscape for a rare disease.

When the COVID-19 pandemic hit, it disrupted all aspects of daily life. Many drug developers were forced to suspend clinical trials because of the challenges of brining participants into medical centers with the risk of infection and the strain on healthcare workers. Palvella Therapeutics, which is developing an experimental therapy for a rare skin condition has been able to navigate the pandemic and continue its clinical study without disruption thanks to recognize the challenge early and adjusting its study plans accordingly. We spoke to Kathy Goin, vice president of development operations for Palvella Therapeutics, about its ongoing study, how it managed to continue unimpeded during the pandemic, and why she expects changes the company made will have a lasting effect on how it conducts clinical studies in the future.

Chris Austin calls himself an evangelist for collaboration when it comes to rare disease drug development. The director of the National Institutes of Health’s National Center for Advancing Translational Sciences said it is essential for rare disease advocates to look beyond their own diseases to recognize commonalities between their conditions and others to find opportunities to collaborate. We spoke to Austin ahead of his keynote address at this year’s Global Genes Rare Drug Development Symposium June 11, about why collaboration is critical to accelerating research, how broadly organizations should think about collaborations, and how patient groups can best work with NCATS to leverage the resources it has.

When Penny Howard’s daughter Harper died in 2016 from the rare neurodevelopmental condition CDKL5 deficiency disorder, Howard and her husband donated her brain and other tissue to research. The donation provided researchers with the first brain of someone who had CDKL5. Today, Harper’s cell lines live at the University of California, San Diego and are used to provide cells to researchers from around the world. Her brain tissue is at the Harvard Brain Tissue Resource Center. We spoke to Howard, founder and president of Hope4Harper, about her daughter’s life and death, the decision to donate her brain, and her journey to becoming an advocate for organ donation.

AMO Pharma is developing drugs for a variety of rare neurologic conditions with a pipeline of experimental therapies seeking to treat Phelan-McDermid syndrome, congenital myotonic dystrophy, and Rett syndrome. The company believes it can advance therapies efficiently by acquiring molecules that have already been studied at either a preclinical or clinical stage and jump starting their development in new indications. We spoke to Michael Snape, chief scientific officer of AMO Pharma, about the company’s approach to drug development, how it selects drugs and diseases to pursue, and its lead therapeutic candidates.

Imago BioSciences is developing therapeutics that change the behavior of malignant blood cells by targeting an enzyme that regulates gene transcription. LSD1 is an epigenetic enzyme that controls how genes are turned on and off in specific cells and plays a key role in the rare bone marrow cancer myelofibrosis. We spoke to Hugh Reinhoff, Jr., CEO of Imago, about myelofibrosis, the company’s experimental therapy bomedemstat to treat the condition, and the case for targeting epigenetic processes to address proliferative diseases of the bone marrow.

Earlier this year Chiesi Farmaceutici established Chiesi Global Rare Diseases, a new business unit to advance research and product development for rare and ultra-rare diseases. The unit, headquartered in Boston, has an initial focus on lysosomal storage, hematologic, and ophthalmologic disorders. We spoke to Giacomo Chiesi, head of Chiesi Global Rare Diseases, about the company’s approach to building its rare disease pipeline, its experimental therapy for Fabry disease, and how it fits in with the company’s broader rare disease strategy.

Rafael Pharmaceuticals is focused on developing therapies that act on the metabolism of rare cancers. It designs drugs that attack regulatory processes that are unique to cancer cells and not found in healthy ones. Its lead drug candidate, devimistat, targets enzymes that are involved in cancer cell energy metabolism and found in the mitochondria of cancer cells. We spoke to Sanjeev Luther, president and CEO of Rafael, about the company’s lead indication of pancreatic cancer, its drug discovery platform, and why it is focused on rare cancers.

When Keith McArthur’s son Bryson was born, he was a happy and loving baby. Soon, though, Bryson began missing developmental milestones and doctors determined he had a neurological disorder. After nearly a decade, Bryson was diagnosed with a variant in his GRIN1 gene. Keith McArthur, who today is CEO and head of science for the CureGRIN Foundation, tells Bryson’s story in an eight-part podcast series produced with the CBC called Unlocking Bryson’s Brain (Hyperurl.co/Bryson). We spoke to McArthur about Bryson, the efforts of the CureGRIN Foundation to find a cure for the condition, and what he hope to accomplish with the podcast series.

There are a number of rare disease where a genetic mutation results in the deficiency of an enzyme or other critical protein that can lead to a progressive or life-threatening condition. Patients have been treated with the chronic administration of recombinant versions of the proteins they lack. While this provides benefit, it requires regular infusions or self-administered shots, is costly, and disruptive. Sigilon is developing what it calls “Shielded Living Therapeutics,” encased cells that can be implanted to provide steady levels of the protein a patient lacks and free them from the need for constant administration of these biologics. We spoke to Rogerio Vivaldi, president and CEO of Sigilon Therapeutics, about the company’s living therapeutics, how it’s able to protect these cells from attack from the immune system, and how they function once inside the body.

Gene therapies to treat retinal diseases promise to reverse blinding conditions, but the approach most gene developers take is to replace a mutated gene underlying a genetic disease with a functional version of that gene. The problem is that this approach can only address a narrow set of patients with each gene therapy. Ocugen, which Is developing gene therapies for eye diseases, believes it can treat a range of rare retinal conditions with a single therapy by introducing a functional gene that has the effect of modifying the expression of multiple genes at once. We spoke to Shankar Musunuri, CEO of Ocugen, about the company’s modifier gene therapy platform, how a single gene therapy can work on multiple eye diseases, and how it may alter the economics for gene therapy for rare eye conditions.

WHIM syndrome is a rare, inherited, primary immunodeficiency disease caused by mutations to the CXCR4 receptor gene. Because of the role CXCR4 plays in the immune system, it is implicated in a number of rare diseases. X4 Pharmaceuticals, a company founded by rare disease pioneer Henri Termeer and other Genzyme alums, is developing a pipeline of CXCR4-targeted therapies. We spoke to Paula Ragan, co-founder, president and CEO of X4, about WHIM syndrome, the role CXCR4 plays in the immune system, and how the company’s experimental therapy Mavorixafor may be able to treat a range of rare conditions.

Syros Pharmaceuticals is developing a platform for targeting the regulatory genome with therapies to address diseases at a fundamental level. At the end of last year, the company entered into a collaboration with Global Blood Therapeutics to develop new therapies for sickle cell disease and beta thalassemia. Under the collaboration, Syros is using its platform to discover drugs that turn on the production of fetal hemoglobin as a way to treat these rare, hereditary, blood disorders. The production of fetal hemoglobin is usually shut down soon after birth. We spoke to David Roth, chief medical officer of Syros Pharmaceuticals, about the collaboration, how Syros’ approach works, and why activating fetal hemoglobin is viewed as a promising approach to treating these genetic blood diseases.

Forma Therapeutics had long been a platform-based drug company that used high-throughput screening to discover new drugs that would be developed by partners. After many years, Forma began transitioning to become a fully integrated therapeutics company focused on rare blood disorders and cancer. It brought in Frank Lee, who had been a senior vice president of global product strategy at Genentech, as CEO to help execute the company’s new plan. We spoke to Lee about why he joined Forma, the company’s program in sickle cell disease, and his vision Forma as a company that develops and commercializes its own medicines.

FSHD is a rare, progressive, muscle wasting disease that affects the face, shoulders, and arms before advancing to the lower body. Like many rare conditions, it is caused by an underlying genetic mutation. Fulcrum Therapeutics is developing an experimental therapy for FSHD, the lead candidate in a pipeline of medicines that target the root causes of genetic diseases. We spoke to Robert Gould, president and CEO of Fulcrum, about FSHD, the company’s experimental therapy to treat the condition, and how he thinks about the company’s broader pipeline.

Prader-Willi syndrome is the most common genetic cause of life-threatening childhood obesity. It is a rare and complex condition that is characterized by unrelenting hunger, or hyperphagia, as well as intellectual disability, short stature, and incomplete sexual development. Millendo Therapeutics is developing livoletide, an experimental, first-in-class therapy that treats hyperphagia by targeting the underlying hormone dysregulation of Prader-Willi syndrome. We spoke to Julia Owens, CEO of Millendo, about Prader-Willi syndrome, the changing development path of livoletide, and what the company has learned as it shifted its focus to a different patient population.

As rare disease patients and advocates seek to raise awareness around the globe for World Rare Disease Day at the end of February, one notable place they will gather is on Capitol Hill in Washington, D.C. It’s become an annual tradition for rare disease advocates to talk face-to-face with lawmakers to bring the abstractions of rare disease down to a human level and speak about the needs patients and their caregivers face. We spoke to Steve Silvestri, director of public policy for the Everylife Foundation for Rare Diseases, about Rare Disease Week on Capitol Hill, the case for patients and caregivers to become advocates, and how they can go about doing so.

Fibroblast growth factors are a group cell signaling proteins that play a critical role in growth and development. They have been implicated in achondroplasia, the most common genetic form of dwarfism, but these growth factors are also involved in a number of rare cancers. QED Therapeutics, a BridgeBio company, is developing infigratinib, an experimental tyrosine kinase inhibitor that targets multiple fibroblast growth factors, for both achondroplasia and certain forms of bile duct and bladder cancers. We spoke to Susan Moran, CEO of QED Therapeutics, about the company’s experimental tyrosine kinase inhibitor, the role fibroblast growth factors play in seemingly disparate rare diseases, and the challenges of learning to work with very different types of patient communities.

Conducting rare disease clinical trials can be challenging because of small and geographically dispersed groups of patients who may face difficulties in travelling to trial sites. Regulatory requirements for cell and gene therapies, even if only administered once, require long-term follow ups that extend for many years and provide an ongoing burden for patients. Jeeva Informatics Solutions is seeking to address those challenges through it harnessing of digital health technologies to bring the trial to the patient. We spoke to Harsha Rajasimha, founder and CEO of Jeeva, about the challenges of conducting rare disease clinical trials, the potential of digital health technologies to address those issues, and how ready regulators and sponsors may be to embrace these technologies to transform the way they conduct clinical trials today.

Terry Pirovolakis became immersed in the world of rare disease after his son Michael was diagnosed with spastic paraplegia 50, an ultra-rare and progressive neurodegenerative disease. Later this month, interdisciplinary teams from around the world will gather as part of a 30-day hackathon to develop therapeutic strategies for Michael’s condition. We spoke to Pirovolakis about Michael’s disease, how the hackathon will work, and why he’s trying to turn this into a sustainable model for other people with ultra-rare diseases to develop treatments for conditions without any.

David Giljohann likens his company’s spherical nucleic acid (SNA) constructs to Koosh balls. But instead of having elastic strings extending from their core, this new class of immunomodulatory and gene regulating drugs are covered with nucleic acids that stick out in all directions. The arrangement allows these oligonucleotides to be taken up by all cell types and can be delivered throughout the body allowing them to overcome some of the limitations of existing nucleic acid therapies. We spoke to Giljohann, CEO of Exicure, about the company’s SNA therapies, how they work, and why they have the potential to treat a wide range of conditions including rare neurological diseases.

Protalix Biotherapeutics plant cell-based platform has been a point of differentiation for the company, a faster and more scalable way of producing protein therapeutics. The company first product, an enzyme replacement therapy for Gaucher disease, offered a proof of its approach. The company is pursuing therapies for Fabry disease and cystic fibrosis, as well as inflammatory diseases, but it is also in the process of rethinking its strategy of biobetters. We spoke to Dror Bashan, CEO of Protalix, about the company’s manufacturing platform, its therapeutic pipeline, and its desire to move toward addressing unmet medical needs.

Antisense pioneer and Ionis Pharmaceuticals Executive Chairman Stanley Crooke has launched a nonprofit to design and deliver custom RNA-targeted therapies free of charge for individual patients with ultra-rare diseases. The organization, n-Lorem Foundation, will leverage Ionis’ technology platform to speed the discovery and development of custom antisense oligonucleotide. We spoke to Crooke about the genesis of n-Lorem, how it will determine whether to work with an individual patient or researcher, and the challenges for regularizing the process of designing n-of-1 therapies for ultra-rare disease patients.

One of the reasons for the clinical failure of drugs is that animal models often fall short as predictors of how a drug will work in humans. StemoniX believes it can cut the time and cost of drug discovery with its microOrgans that are engineered from human induced pluripotent stem cells. These microOrgans can be used for high throughput human drug screening without the need for drugs to enter a human subject. We spoke to Ping Yeh, CEO of StemoniX, about the company’s technology platform, how it works, and its recent agreement with the AI company Atomwise to discover and develop small molecule candidates to treat the rare neurological condition Rett syndrome.

In December, Castle Creek Pharmaceutical Holdings completed its acquisition of Fibrocell. The deal brought together two companies developing therapies for rare skin disorders. We spoke to John Maslowski, CEO of the combined company, about its late-stage gene therapy in development for recessive dystrophic epidermolysis bullosa, how it differs from what is conventionally thought of as gene therapy, and what the acquisition does to advance the pipeline of the two companies.

ALS is a progressive neurodegenerative disease. As motor neurons die, people with the condition grow weaker and lose motor function. For most, death occurs within three to five years of diagnosis. Brainstorm Cell Therapeutics is conducting a phase 3 clinical trial of its autologous stem cell therapy that programs cells taken from patients to produce neuro-protective factors that promote the survival of neurons. We spoke to Ralph Kern, chief operating officer and chief medical officer of Brainstorm Cell Therapeutics, about ALS, the company’s late-stage experimental therapy, and how its approach may provide benefits for patients with other neurodegenerative disease.

Earlier this month, Origin Biosciences initiated a rolling submission with the U.S. Food and Drug Administration for approval to market an experimental therapy to treat the ultra-rare metabolic condition molybdenum cofactor deficiency (MoCD) Type A. The condition manifests itself shortly after birth and leads to difficulty feeding and intractable seizures. Children with the condition have a median survival of three years and those who live longer suffer irreversible damage to their central nervous system. The rolling submission comes about a year and a half after BridgeBio acquired the therapy from Alexion Pharmaceuticals and formed Origin Biosciences to develop it. We spoke to Neil Kirby, CEO of Origin, about MoCD, how its synthetic enzyme co-factor works to treat it, and the plans for Origin beyond the submission for approval.

There is no clear agreement as to what constitutes a rare disease, the actual number of rare diseases, and how individual rare diseases are defined. The lack of clarity on the matter is not just an academic issue. The consequences of this, say researchers, is that it slows the diagnostic process and impedes the development of needed therapies for these conditions. In a recent commentary in the journal Nature Reviews Drug Discovery, Melissa Haendel and her co-authors discuss their efforts to characterize, define, and harmonize the definitions of rare disease through the Monarch Disease Ontology initiative. We spoke to Haendel, associate professor of medical informatics and clinical epidemiology at the Oregon Clinical and Translational Research Institute, about the problem with the different way organizations characterize and define rare diseases, the challenges of aligning these definitions, and why harmonization is critical for making progress in diagnosing and treating these conditions.

Drug developers and regulators are rapidly expanding the use of real-world evidence to develop rare disease therapies, but a new report finds payers are far less enthusiastic about incorporating such data in evaluating the value of therapies. The report from Syneos Health found payers have concerns about a lack of standards and have gaps in their understanding. We spoke to Meg Alexander, head of the reputation and risk management practice for Syneos Health, about the report, the important role real-world evidence can play in rare disease drug development, and why payers are moving slower than drug developers and regulators to embrace real-world evidence.

Rich Horgan was attending Harvard Business School when he started reaching out to leading researchers to learn about his brother Terry’s condition Duchenne muscular dystrophy and what could be done to accelerate efforts to find a cure. Horgan was taken with the work of Timothy Yu to develop a customized therapy for a young girl with a form of the rare neurological condition Batten disease and founded the nonprofit organization Cure Rare Disease to develop customized therapies to treat patients with rare, genetic conditions. We spoke to Horgan, founder and president of Cure Rare Disease, about the organization, his efforts to develop a treatment for his brother, and what it will take to scale the process to address the needs of a large group of patients with rare, genetic conditions.

Expanded access—a means of allowing people with serious and life-threatening conditions who fail to meet the enrollment criteria of a clinical trial to gain access to experimental therapies —has become an area of growing interest among the rare disease community. Though so-called right-to-try legislation has allowed patients to bypass regulators, it has done little to address the true obstacles patients face in getting access to these therapies. The Expanded Access Summit, which will be help January 27 to 29 at the National Press Club in Washington, D.C., will bring together regulators, drug developers, patients, and other stakeholders interested in expanded access. We spoke to Jess Rabourn, CEO of WideTrial and executive producer of the Expanded Access Summit (easummit.net), about the promise of expanded access, how it can be used to improve the clinical development of therapies, and how to address some of the remaining barriers to patient access of experimental therapies.

When Kyle Bryant was diagnosed with the rare neuromuscular disease Friedreich's ataxia, it upended his sense of himself and his future as he began to wrestle with feelings of anger and depression. His life changed, though, when he read about a man with multiple sclerosis and his use of a recumbent trike, an adult-sized tricycle with a reclined seat. Bryant was inspired and shortly planned a cross-country bike trip with his father to raise money for Friedreich's ataxia research, a journey he chronicled in his book “Shifting into High Gear.” We spoke to Bryant, director of Ride Ataxia at the Friedreich's ataxia Research Alliance and co-host of the Two Disabled Dudes podcast, about his bike journey, how it changed his relationship with his disease, and how it gave rise to his work as an advocate.

Keisha Greaves was studying for a career in fashion and business when she was diagnosed with limb-girdle muscular dystrophy, a rare and progressive neuromuscular condition. Rather than let her disease sidetrack her entrepreneurial vision, she has used it as a source of inspiration. She launched Girls Chronically Rock to produce T-shirts and adaptive clothing that celebrates and empowers people with chronic diseases. We spoke to Greaves about her experience with chronic illness, her vision for Girls Chronically Rock, and her efforts to bring adaptive wear to mainstream retailers.

Seth Rotberg and Kristina Wolfe have each felt the isolation of entering adulthood in the shadow of rare and chronic disease. Rotberg, whose mother was diagnosed with Huntington’s disease, had genetic testing as a college student that showed he too will develop the neurodegenerative condition. Wolfe has grown up with type 1 diabetes. The two founded Our Odyssey to help young adults connect, find social and emotional support, and help them improve their quality of life. We spoke to Rotberg and Wolfe about their own experiences, why they created Our Odyssey, and the unique psychosocial issues people with rare and chronic diseases face in transitioning to adulthood.

Cristol O'Loughlin grew up with three older brothers with the rare lysosomal storage disorder MPS II, or Hunter syndrome. The experience of seeing the demands on her mother led her to create Angel Aid Cares, an organization that seeks to support and connect caregivers, and help them learn to care for themselves while caring for others. We spoke to O’Loughlin about the challenges caregivers face, why they often neglect their own needs, and how her organization seeks to help them.

Disorder: The Rare Disease Film Festival features films from around the world that capture the challenges of life with a rare disease. Launched in Boston in 2017, the festival will be held in San Francisco November 9 and 10 at the UCSF Mission Bay Campus. We spoke to Bo Bigelow, co-founder of Disorder, about what’s showing at this year’s festival, the power of film to raise awareness about rare disease, and how the event is intended to foster connections between patients and researchers.

Last month, Deep Genomics garnered headlines when it declared that it had nominated the industry’s first artificial intelligence-discovered therapeutic candidate. The experimental therapy is intended to treat Wilson disease, a rare and potentially life-threatening condition. The target for the therapy was also identified by the company’s AI platform and Deep Genomics said it was able to identify the target and drug candidate in less than 18 months. We spoke to Brendan Frey, founder and CEO of Deep Genomics, about the company’s AI platform, why it is focused on genetic disease, and the case for the company’s approach to drug discovery.

Shane Burcaw and Hannah Aylward, known to YouTube viewers as Squirmy and Grubs, often find people have trouble comprehending their relationship. Burcaw, who is disabled as a result of spinal muscular atrophy, weighs just 65 pounds and has limited physical abilities. As the title of his latest book explains, “Strangers Assume My Girlfriend Is My Nurse.” We spoke to Burcaw and Aylward about their relationship, their encounters with others, and their efforts to shatter misconceptions about the ability for disabled people to have a love life.

Jeremy Levin’s high-profile success at building the pipeline at Bristol-Myers Squibb through deal-making and driving the company into immunotherapies, has given him the ability to take virtually any job he’d like in the biopharmaceutical sector. Given that, it may seem surprising the Big Pharma executive chose to become CEO of a development-stage company focused on rare neurological conditions. We spoke to Levin, CEO of Ovid Therapeutics, about why he took the job, the conditions the company is targeting, and whether his interest in rare diseases will shape the agenda of BIO now that he serves as chairman of the trade group.

Jennifer and Tracy VanHoutan lost two children in less than two years to CLN2 Batten disease, a rare, genetic, neurodegenerative condition that slowly robs children of their abilities before taking their lives. The VanHoutans founded Noah’s Hope to create awareness, raise money to fund research, and eliminate policy barriers to bringing therapies to patients. Despite their loss, they continue to advocate and push for treatments. At this year’s Global Genes Rare Patient Advocacy Summit in San Diego September 18 to 20, the two will be honored with a 2019 RARE Champion of Hope Award for their advocacy work. We spoke to the VanHoutans about CLN2 Batten disease, their advocacy work, and their ability to fight on after the loss they suffered.

When David Fajgenbaum was in medical school, he became stricken with a rare autoimmune disease that nearly killed him. Though he recovered, he would suffer recurring, life-threatening flares only to discover the poor state of research into condition. Fajgenbaum chronicles his rare disease journey and his efforts to drive research and find treatments in his new book “Chasing My Cure: A Doctor’s Race to Turn Hope into Action.” Fajgenbaum, who is executive director of the Castleman Disease Collaborative Network, will be featured at this year’s Global Genes Rare Patient Advocacy Summit, which begins in San Diego September 18. Ahead of the summit, we spoke to him about his experience as a rare disease patient, his efforts to find treatments for his conditions, and how his innovative approach to developing a patient-driven research agenda has provided a roadmap for other rare disease organization to follow suit.

Journalist and best-selling author Susannah Cahalan, ahead of her keynote address at the Global Genes’ RARE Patient Advocacy Summit September 18 in San Diego, discusses about her diagnostic odyssey, the critical role the support of her loved ones made, and what allowed the doctor who diagnosed and treated her to succeed where others had failed.

Nancy Patterson was diagnosed 32 years ago with Graves’ disease, a rare autoimmune condition that causes the thyroid to become overactive and can lead to a range of health complications. Patterson, a practicing mental health counselor, founded the Graves’ Disease and Thyroid Foundation, which she led for nearly 20 years. In her counseling role, she has worked with patients and families across the country and has been a proponent of the important role support groups can play in healing and educating people, particularly in a condition where patients are otherwise unlikely to meet others with the same disease. We spoke to Patterson about Graves’ disease, her own journey as a patient and advocate, and the benefits support groups can provide.

Epigenetics is the study of the regulatory system that controls how genes are turned on or off. In certain cancers, the proteins that regulate gene expression become dysregulated and incorrectly activate or deactivate genes, which can lead to cancer. Salarius Pharmaceuticals is targeting the epigenetic causes of cancer, including rare pediatric cancers. We spoke to David Arthur, CEO of Salarius about epigenetics, the rare cancer Ewing sarcoma, and company’s lead drug candidate to treat the condition.

Pediatric and primary hyperoxaluria is a rare genetic condition that causes over absorption of oxalate, a compound found in many foods. Too much oxalate can lead to the formation of kidney stones and cause progressive damage of the kidneys. Allena Pharmaceuticals is developing an oral enzyme to treat both the rare form of hyperoxaluria and a more common form of the condition. We spoke to Louis Brenner, CEO of Allena, about the company’s experimental therapy to treat hyperoxaluria, it’s platform for delivering enzymes orally, and the potential to apply the technology beyond kidney diseases.

Casimir Trials is a contract research organization that is seeking to bring patient and caregiver perspective into the clinical trials process. It’s working with drug developers to create endpoints and measures that can provide rigorous and quantifiable means of demonstrating whether an experimental therapy provides meaningful improvements to a patient’s quality of life. We spoke to Christine McSherry, co-founder and CEO of Casimir Trials, about the challenges of developing patient-centric outcome measures, how technology is allowing for the capture of real-world evidence, and how Casimir began with a challenge from the FDA’s Center for Drug Evaluation and Research Director Janet Woodcock to a mother and patient advocate concerned over the use of endpoints that could obscure the value of needed drugs to rare disease patients.

Idiopathic pulmonary fibrosis is a serious, life-limiting lung disease characterized by fibrosis and scarring of lung tissue. Patients generally live only about three to five years after a diagnosis. Approved therapies can slow down the progression of the disease, but no available therapies halt or reverse it. The only curative therapy is a lung transplant, an option that is available to only a small subset of patients. Promedior is developing an experimental therapy it believes may not only halt the disease, but reverse it. We spoke to Jason Lettmann, CEO of Promedior, about the company’s experimental therapy, how it works, and why it may have the potential to treat a wide range of fibrotic diseases.

Patients with rare diseases often have a complex constellation of symptoms that require the care of multiple specialists. Getting access to the needed mix of physicians and counselors can represent geographic and scheduling challenges for patients and caregivers and create difficulties in coordinating care between specialists. One approach to addressing these needs has been the development of centers of excellence that can provide comprehensive and coordinated care for patients with experts in their condition. We spoke to Amber McCarthy, a Huntington’s disease social worker with UTHealth/UT Physicians in Houston, about the Huntington’s Disease Society of America’s Centers of Excellence, how these centers operate, and how they are transforming care for Huntington’s disease patients.

Mitochondria are the powerhouses of the cell and play a central role in a number of rare diseases. Mitochondria have their own DNA and Minovia Therapeutics is seeking to develop cell therapies designed to repair damaged mitochondrial DNA using autologous stem cells that have been enriched with blood-derived mitochondria. We spoke to Natalie Yivgi Ohana, co-founder and CEO of Minovia, about the company’s mitochondria augmentation therapy, how it works, and why it may point the way for treating more common conditions, such as Alzheimer’s disease.

Earlier this year Passage Bio announced its launch with $115.5 million in funding and a group of founders with a strong pedigree. The company’s founders include gene therapy pioneer James Wilson, pharmaceutical industry veteran Tachi Yamada, and former Alexion executive and OrbiMed Venture Partner Stephen Squinto. One point of distinction for the company is its unique partnership with the University of Pennsylvania and its Gene Therapy Program, which gives it access to technology developed there, as well as its preclinical translational science capabilities. We spoke Squinto, interim CEO of Passage Bio, about the company’s focus on rare monogenic CNS diseases, its relationship with Penn, and why he’s confident with strong data, discussion with payers will not be a problem.

AGTC is developing gene therapies to treat patients with rare inherited eye conditions. It has multiple programs it is advancing to restore visual function in patients with diseases that threaten to leave them blind. One issue that has emerged, though, is finding the right measures and endpoint for its clinical studies and getting the U.S. Food and Drug Administration to recognize the traditional endpoints and measures used for eye diseases may not be well suited for all of these conditions. We spoke to Sue Washer, CEO of AGTC, about the company, the indications it is pursuing, and its efforts to find and use more appropriate endpoints for its studies.

Avidity Biosciences is pioneering antibody oligonucleotide, a new class of therapeutics that marry the target selectivity of monoclonal antibodies with the precision of genetic medicine. The company is focusing on treatments for rare muscle disorders including myotonic dystrophy type 1 and Duchenne muscular dystrophy. We spoke to Art Levin, executive vice president of research and development at Avidity Biosciences, about the company’s therapeutic approach, why it’s focusing on rare muscle disorders, and the path forward for its therapies.

Global Genes Rare University is rolling out a new online course aimed at helping rare disease patients and families understand the world of genetics. The course, which is free, starts with the basic genetic concepts for rare disease, and them moves to family and heredity, genetic testing, and scientific advances. We spoke to Holly Snyder, a lead editor on the Rare University genetics course and senior genetic counselor at Illumina, about what rare disease patients and their families should understand about genetics, genetic testing, and why genetic literacy matters.

For rare disease patient groups seeking to drive research toward the development of therapies, many obstacles exist. By setting an overarching research agenda, driving collaborations among researchers, and sharing what is learned, patient groups are getting the most out of limited budgets and accelerating the time it takes to develop new treatments. The newly announced Rare As One Project from the Chan Zuckerberg Initiative seeks to help rare disease patient organizations apply the collaborative research model and improve on it. We spoke to Tania Simoncelli, science policy director of the Chan Zuckerberg Initiative, about the program, how it works, and what the organization hopes the long-term effects of its efforts will be.

Wendy Chung and her lab have proven a talent for identifying new rare diseases. She and her team have discovered more than 44 genetic conditions to date. But Chung, a professor of pediatrics and medicine at Columbia University and New York-Presbyterian Hospital, and director of the clinical genetics program at Columbia University, is driving beyond discovery to help patients find therapeutic alternatives for these conditions at Columbia University’s Center for Rare Pediatric Genetic Diseases. We spoke to Chung about the Center, how it works to find new treatments for rare diseases, and what hopes she has for scaling and accelerating the search for new therapies treat rare diseases with small populations.

The emotional impact a rare disease can have on siblings of children with these conditions can be significant. A sibling voices survey evaluating the psychological effects of growing up with a sibling with severe epileptic encephalopathies presented at the European Congress on Epileptology last year suggests these children may be as risk for anxiety or depression. We spoke to Lauren Schwartz, a psychologist at the Rehabilitation Medicine Clinic at UW Medical Center, about the study, what it found, and what parents should take away from it.

Early diagnosis and intervention can improve outcomes for children with autism spectrum disorder but arriving at a diagnosis can be difficult at an early age. To diagnose the condition, doctors have relied on behavioral tests and the average age of diagnosis in the United States is more than 4 years. NeuroPointDX has developed a diagnostic test that looks at metabolic imbalances in the blood that can diagnose a child with the condition as young as 18 months. We spoke to Elizabeth Donley, CEO of Stemina Biomarker Discovery and NeuroPointDX, about the condition, how the company’s test works, and what it might suggest about the biology of the condition.

Natural history studies track the course of a disease over time, helping researchers understand the different ways a condition may manifest itself and progress. These studies can also provide insight into whether patient populations should be divided into subtypes for more targeted therapeutic approaches. Such data often represents a foundational understanding of a disease that can play an essential role in the design of clinical trials, helping investigators determine appropriate protocols and select endpoints for a study. In some cases, natural history studies can serve as an alternative to a placebo arms of a clinical trial. Ahead of the upcoming Rare Drug Development Symposium, we spoke to Erika De Boever, deputy director of the Orphan Disease Center at the University of Pennsylvania School of Medicine, about natural history studies, the different types that exist, and why they play such a critical role in clinical trials for rare diseases.

When Lara Pullen’s son was diagnosed with Prader-Willi syndrome, she began to dive into the scientific literature about the rare condition. Pullen, a scientist and co-founder of the Chion Foundation, discovered that pitolisant, a recently approved drug for narcolepsy, might benefit patients with Prader-Willi. Working with her Chion co-founder Maria Picone, who developed an online data-gathering platform for patient-reported outcomes, they tracked the effects of the drug in three patients. In a clinical vignette published in the Journal of Pediatric Pharmacology and Therapeutics in April, they reported their findings. We spoke to Pullen about her efforts, the value of patient-reported outcomes, and why the work she’s done suggests the need for a more neurologically-based approach to treating Prader-Willi.

One reason for the extended diagnostic odyssey that rare disease patients face is that doctors are often unfamiliar with the rare conditions they may have. In addition, doctors are trained to think of the likeliest explanation for a patient’s symptoms, which may be similar to those of more common diseases. London-based Mendelian is working to bring machine learning to the rare disease diagnostic process as a way to identify patients whose symptoms may suggest they have an underlying rare genetic disease and provide a path forward to finding an answer. We spoke to Rudy Benfredj, co-founder and CEO of Mendelian, about the diagnostic challenge rare disease patients face, the company’s platform technology, and whether he thinks we’ll see an end to the diagnostic odyssey anytime soon.

Children awaiting adoption with a rare disease may go untreated or receive minimal treatment. If they go unplaced, they may face life in a long-term care facility, or nursing home. Gift of Adoption is a nonprofit that provides adoption assistance grants to help vulnerable children find a permanent home and the chance to thrive. We spoke to Pam Devereux, CEO of Gift of Adoption, about the cost of adoption, how her organization works, and the need it is seeking to address.

April 29 is Undiagnosed Rare Disease Day. It is a day when advocates raise awareness among the general public and policy makers about the emotional, physical, and financial impact living with an undiagnosed rare disease has on patients and their families. Ahead of this year’s Undiagnosed Rare Disease Day we spoke with Ava Szajnuk, an 11-year-old undiagnosed rare disease patient and advocate, about how her condition impacts her daily life, and the work she’s done as an advocate.

The Foundation for Angelman Syndrome Therapeutics Australia says it has created a Global Angelman Syndrome Registry that gives parents and caregivers the power to drive the collection of data. Its goal is to make the registry the largest collection of information about the neurological disorder to date and use it to inform the research for new therapies by providing insights into the developmental progress, medication, and seizure management related to the condition. One unique aspect of the registry is that it uses an open-source framework developed by Centre for Comparative Genomics at Murdoch University in Perth, Australia. We spoke to Meagan Cross, chairperson of the Foundation for Angelman Syndrome Therapeutics Australia, about Angelman syndrome, the efforts to build the registry, and why the use of an open-source platform can help address barriers rare disease organization face in creating registries.

Rett syndrome is a genetic disorder that mostly affect girls and is often misdiagnosed as autism, cerebral palsy, or non-specific developmental delay. A study recently published in the journal Neurology reports encouraging results from a mid-stage clinical trial for an experimental therapy to treat the condition. The patient organization Rettsyndrome.org played a key role in identifying the potential application for the drug in Rett syndrome and provided early funding. We spoke to Steve Kaminsky, chief science officer of Rettsyndrome.org about the drug, the role his organization has played in its development, and how it may one day change the landscape for patients with the condition.

Sickle cell disease is the most common inherited blood disorder in the United States. People with the condition have sickle-shaped red blood cells and these misshaped cells can block the flow of blood and oxygen to organs throughout the body. These blockages can cause severe pain, organ damage, and strokes. While the disease is well understood, treatment options today are limited and obtaining proper care can be complicated by healthcare workers' lack of understanding of the disease, racism, and a misconception that the condition only affects African Americans. We spoke to Marqus Valentine, co-founder of Sick Cells, and Doris Polanco, a member of the Sickle Cell Thalassemia Patients Network, about sickle cell disease, their experiences with the condition, and how ignorance about the disease affected their care.

A number of rare, genetic diseases including Huntington’s disease and myotonic dystrophy belong to a group of conditions known as repeat expansion disorders. Though it's normal to have pieces of repeating genetic code, these diseases involve an abnormally high number of repeats that result in the production of toxic proteins. NeuBase Therapeutics is using its platform technology to produce antisense drugs that it believes have distinct advantages over existing antisense drugs today. NeuBase recently announced a reverse merger with Ohr Pharmaceutical that propels the pre-clinical stage company onto the Nasdaq market. We spoke to Dietrich Stephan, CEO of Neubase, about repeat expansion disorders, the company’s platform technologies, and why he believes it has distinct advantages over existing therapies that target RNA.

Transthyretin is a protein found in the blood. Its name reflects its function, which is to transport thyroxine and retinol. In the case of a number of rare conditions, the protein becomes unstable and misfold, causing it to accumulate as toxic protein deposits in the heart or peripheral nerves. Eidos Therapeutics, a subsidiary of BridgeBio, is developing an experimental small molecule drug that binds and stabilizes transthyretin in the blood. We spoke to Jonathan Fox, chief medical officer of Eidos, about the rare diseases it is targeting, the treatments available today, and how it may change the landscape for these conditions.

The complement system, part of the immune system, has long been used as a target for interventions in certain rare disease. Apellis Pharmaceuticals is developing therapies to treat rare blood and kidney diseases, but by targeting a different part of the complement system than available therapies do today. We spoke to Cedric Francois, co-founder, president and CEO of Apellis, about the complement system, Apellis’ approach, and why he thinks this will lead to better therapies for these rare diseases.

One of the challenges rare disease advocates face in advancing research and treatments is finding the patients needed to understand the natural history of a disease and participate in clinical trials. That’s true for cavernous angioma, a formation of abnormal blood vessels in the brain and spinal cord with leaky walls that can cause seizures, stroke symptoms, hemorrhages, and headaches. The Angioma Alliance, though, has hit on an unusual strategy to find patients with the condition to build its registry as clinical trials for potential treatments get under way. We spoke to Connie Lee, president and CEO of the Angioma Alliance, about the condition, the start of the first clinical trial for a potential treatment, and why the history of a family who came to New Mexico in 1600 is helping identify patients with the condition today.

As CEO of Ionis Pharmaceuticals, Stanley Crooke has been a pioneer in the development of antisense drugs and oversees one of the industry’s largest and most advanced pipelines. Antisense drugs are compelling for rare diseases because of their ability to selectively target specific RNA sequences. These drugs, such as the company’s treatment for spinal muscular atrophy, Spinraza, are transforming the outlook for rare disease patients. We spoke to Crooke about Ionis’ ability to succeed as a platform technology company, why he thinks gene therapy will not pose a threat to the company’s antisense platform, and why he sees the value of these therapies withstanding growing pricing pressures.

It was about ten months ago that Orchard Therapeutics acquired the gene therapy portfolio of GSK, expanding its pipeline and giving it its first approved therapy. We spoke to Orchard CEO Mark Rothera about his company’s approach to gene therapy, its pipeline, and what he sees as the biggest challenges as Orchard moves towards commercializing its therapies.

Harsha Rajasimha was a post-doctoral researcher at the National Institutes of Health when he lost a newborn child to a rare disease. As he entered the world of patient advocacy, he connected with rare disease patients in his homeland of India. Discussions he had there led him to co-found the Organization for Rare Diseases India and the Organization for Rare Diseases India, USA; an effort to bridge the gulf between rare disease patients in the two countries. We spoke to Rajasimha about the rare disease landscape in India, the opportunities for India to drive development of new therapies for rare disease, and what his organizations are doing to foster cooperation between rare disease patients in India and the United States.

The regenerative medicine sector won major product approvals, advanced a growing pipeline of therapies in development, and enjoyed a surge of investment in 2018. As excitement grows about the potential of these therapies, the industry is also wrestling with complex policy issues that could determine how sustainable these businesses will be and whether patients will ever get to benefit from the potential cures that may soon be within reach. We spoke to Matt Patterson, chairman of the Alliance for Regenerative Medicine, about the state of the industry, ongoing debates about pricing and payment models, and what the industry will need to do to educate patients and policymakers about this emerging area of medicine.

The microbiome, the community of bacteria that live within and on our bodies, has become an area of increasing interest to drug developers, who see the potential to both target these microorganisms and exploit them for therapeutic benefit. Scioto Biosciences has developed a biofilm platform that it believes can better deliver and protect beneficial bacteria to treat disease. The lead indication the company is pursuing is necrotizing enterocolitis, a rare condition primarily afflicting premature newborns that causes portions of the bowel to die. We spoke to Joe Trebley, CEO of Scioto, about the microbiome, the company’s platform technology, and how it is exploiting something usually thought of in the context of pathogenic bacteria to help beneficial bacteria thrive.

Tiburio Therapeutics emerged from the orphan drug accelerator Cydan at the start of 2019. The company is developing two clinical stage compounds for rare endocrine disorders that it licensed from Ipsen. We spoke to Tiburio Therapeutics CEO Abraham Ceesay, about rare endocrine disorders, the company’s pipeline, and the case for Cydan’s business model.

Aspa Therapeutics is a subsidiary of Bridge Bio that was created to develop a gene therapy to treat Canavan disease, a progressive and fatal neurological disorder for which there is no approved therapy. Canavan is caused by a genetic mutation that results in an enzyme deficiency. We spoke to Eric David, CEO of Aspa, about the condition, the company’s experimental gene therapy, and the benefits of Bridge Bio’s approach.

Patient-led collaborations are transforming drug discovery and development in rare disease. How they are doing this will be the topic of a panel discussion at the 2019 Biotech Showcase in San Francisco January 8 at 4:30 p.m. Ahead of that panel, we spoke to Walt Kowtoniuk, principal at Third Rock Ventures and moderator of the panel to discuss the challenges of rare disease drug discovery and development, how patient-led collaborations are addressing these challenges, and how patient involvement can change the risk profile of drug development to attract drug company partners and investors. For information on the panel or to register, go to www.globalgenes.org/rareinthesquare

Last month, the U.S. Food and Drug Administration approved Sobi’s Gamifant to treat HLH, an ultra-rare condition characterized by hyperinflammation with high morbidity and mortality. The approval strengthens Sobi’s immunology franchise in the United States. We spoke to Rami Levin, president of Sobi North America, and Carol Satler, vice president of medical affairs for Sobi, about HLH, the significance of the Gamifant approval, and how it fits in with the company’s broader strategy.

Collaboration is critical to addressing problems faced by the rare disease community, but too often collaborations between advocacy organizations turn sour because of miscommunication, a lack of trust between partners, or when unnecessary competition trumps cooperation. A group of rare disease advocacy organizations, including Global Genes, earlier this year launched the THRIVE initiative (https://www.thriveforrare.org/), an effort to foster cooperation between rare disease groups and address the behaviors that too often undermine the work of the community. We spoke to Amy Brin Miller, executive director of the Child Neurology Foundation and co-founder of THRIVE, about the initiative, how it came about, and the problem it’s trying to address.

Prader-Willi syndrome is a rare genetic disease with many effects, but it is characterized by an insatiable drive to eat that leads to overeating and obesity. Soleno Therapeutics is in late-stage clinical testing of a treatment for the intense hunger and overeating in patients with Prader-Willi. We spoke to Anish Bhatnagar, CEO of Soleno, about its experimental therapy, how it works, and why it may have application in a broader range of indications.

The U.S. Food and Drug Administration recently granted gene therapy developer RegenxBio Orphan Drug designation for its experimental gene therapy to treat CLN2 disease, a form of Batten disease, a rare and deadly condition that progressively robs children of their abilities until they die. The gene therapy is one of 12 clinical programs and 20 partnered programs RegenxBio is advancing. We spoke to Ken Mills, CEO of RegenxBio, about CLN2 disease, the company’s next-generation gene therapy platform, and why he believes it offers advantages over other AAV gene therapies.

LBSL, a rare genetic disorder that affects the brain and spinal cord, was first identified in 2004. While there are no treatments available today, researchers are working to understand the condition and develop therapies. One ongoing study at Kennedy Krieger Institute is using digital health technologies to remotely test people with the condition and provide a roadmap towards a therapy. We spoke to Ali Fatemi, director of the Moser Center for Leukodystrophies at the Kennedy Krieger Institute, about the study, his use of digital health technologies, and their potential to transform the way researchers conduct clinical trials.

Many rare disease organizations are resource constrained and depend on the kindness of volunteers to provide specialized services and capabilities that they may not have in-house. Sean Gordon, a high-tech sales and marketing specialist, discovered the need after he was diagnosed late in life with a rare disease. His solution has been to create the Rare Funding Team, a free service that matches rare disease organizations to volunteers. We spoke to Gordon about his own diagnosis, the work he does through the Rare Funding Team, and the need he is trying to fill.

When the Hereditary Neuropathy Foundation set up a patient focused drug development meeting with the FDA, it knew that patients with Charcot-Marie-Tooth disease face difficulty providing written comments because of the impact of the disease on their ability to write or type. Working with a technology company, the organization was able to gather patient feedback using voice technology that allowed them to report comments over the phone through an automated system. We spoke to Allison Moore, CEO of the Hereditary Neuropathy Foundation, about the use of this technology, how it works, and why it may benefit patients with many other conditions.

When Jon Miller’s son was born doctors failed to diagnose a rare and deadly medical condition despite using newborn screening that was supposed to detect it. Doctors told him his infant was going to die. His son was diagnosed correctly in time as having tyrosinemia, a genetic disorder characterized by elevated blood levels of the amino acid tyrosine, the result of an enzyme deficiency. The experienced led Miller to create NOTA, the Network of Tyrosinemia Advocates. We spoke to Miller about his advocacy, the need for addressing a problem with newborn screening, and why from the earliest days his organization has fought for access to needed medications for tyrosinemia patients around the world.

Sickle cell disease is a rare, genetic condition that causes red blood cells to become misshapen and damaged. The condition activates immune cells and blocks blood flow in capillaries, causing injury to many organs and pain daily. Imara is developing an experimental therapy that can prevent the sickling of the red blood cells and also reduce the adhesion of white blood cells to reduce blockage of the blood vessels. We spoke to Rahul Ballal, CEO of Imara, about the therapy, the class of drugs it belongs to, and what the company has done to enroll a population of patients traditionally underrepresented in clinical trials.

When Sean Baumstark was 25, he was diagnosed with Friedreich’s ataxia, a rare, debilitating and life-shortening disease. His doctor advised him to avoid activities where balance was critical, such as biking, hiking, or running. He told Baumstark he should move to a home without stairs and install handrails. A month later Baumstark bought a bike and set off on a 650-mile trek from his home in Sacramento to Las Vegas. Among the many things he does today, his De:terminence program provides people with rare conditions training, assistance, and equipment to complete challenging physical feats, such as climbing mountains or running in marathons. We spoke to Baumstark about his own rare disease diagnosis, how it became a turning point in his life, and how he learned to embrace life so fully.

Despite accelerated pathways for the development and approval of rare disease therapies, significant challenges remain for companies wishing to bring new treatments to market. Mallory Factor, CEO of IntraBio, recently testified at a U.S. Senate Subcommittee hearing and argued that the programs in place today fail to address the needs companies like his have for timely and early interactions with the U.S. Food and Drug Administration when developing therapies for diseases afflicting small populations of patients. We spoke to Factor about his recent testimony, the issues companies like his face, and what he’d like to see done to address the problem.

Two attorneys specializing in regulatory law recently proposed the creation of an FDA Rare Disease Center of Excellence to better allow the agency to address the challenges of advancing and reviewing rare disease products. The proposal, advanced by Hyman, Phelps & McNamara’s Director Frank Sasinowski and Associate James Valentine, also calls for the creation of deputy directors of rare disease at various FDA divisions and the creation of a rare disease advisory committee made up of external experts. We spoke to Valentine about the proposal, why these measures are needed, and the early response from one key figure at the FDA.

This summer, elite runner Dave Proctor set out on a 4,500-mile run across Canada to break a Guinness World Record and raise $1 million to support the Rare Disease Foundation. Proctor’s son Sam has an ultra-rare neurological condition. Though an injury cut Proctor’s run short, it did ignite the imagination of the public and catch the attention of legislators. We spoke to Proctor about the run, the rare disease landscape in Canada, and what his plans are going forward for his organization Outrun Rare.

Collaborations play a critical role in advancing potential treatments for a rare disease and can take many forms. In some cases, they may involve a single researcher engaging with a single patient, while more complex ones may be multi-organizational alliances that include drug developers, academic institutions, and patient advocacy organizations. We spoke to Hans Schlecht, a physician who has conducted research and the father of a son with an ultra-rare disease, about the importance of collaborations, how patients can engage researchers, and what they can do to ensure the best returns for their efforts.

Seeking treatment for a rare disease can be complicated by the poor understanding clinicians may have of a given condition and variations in the way they diagnose, treat, and monitor a specific disease. One way to ensure patients receive the best care is through the implementation of clinical standards. We spoke to Kathi Kinnett, vice president of clinical care for Parent Project Muscular Dystrophy, about the process of establishing clinical standards for a rare disease, the role patients should play in that process, and what steps can be taken to ensure that clinics adhere to them.

A few years ago, Kavi Gandhi’s parents told him that they had become overwhelmed with the demands of running the foundation they had started to fund research for I-Cell disease, a condition that his older brother Yash died from at the age of 9. Kavi told his parents he didn’t want them to close the foundation and offered to take on some of the responsibilities of running it. Since them he has become a fierce advocate. He’s organized events, raised money, and maintained an active presence on social media for the organization. In recognition of his work, Global Genes named Gandhi the 2018 Global Genes’ RARE Champion of Hope for Teen Advocacy. We spoke to Gandhi, development and communications coordinator for the Yash Gandhi Foundation, about his decision to take a central role at the foundation, the perspective he brings to the work as someone who lost an older brother to a rare disease, and his life as a teen advocate.

People with rare and chronic conditions often become so focused on the treatment of their physical ailments that the psychological and emotional aspects of their diseases can be neglected. Allison Fine, a clinical social worker, founded the Center for Chronic Illness in Seattle to provide professionally-led support groups to people with ongoing health challenges. We spoke to Fine about her work, the psychological toll rare conditions can take, and how these patients can go about finding help they need.

When Mary Beth Campbell’s son Calvin was diagnosed with Bloom Syndrome, a rare genetic disease that can lead to the development of cancer, she found a patient community that had mobilized in fits and starts. There had been efforts to create a patient registry and collect biosamples, but it was not consistently maintained. There was no natural history study of the disease, no animal model for it, no validated target for drug development, and no strong patient community. We spoke to Campbell about her efforts to catalyze the Bloom Syndrome community around a research agenda, how they looked to other rare disease communities to gauge their weaknesses, and how they prioritized what needs to be done.

When Hillary Savoie was pregnant, an ultrasound concerned her doctors that her child might be born with a genetic disease. When her daughter Esmé was born, despite the health problems she faced, Savoie resisted having genetic testing performed. When her daughter was eventually tested, it did not provide clarity. Eventually four suspect genes were identified through various tests. Savoie, founder of The Cute Syndrome Foundation, has chronicled her experiences with Esmé in two short memoirs "Around and into the Unknown" and "Whoosh". She discussed experiences as the mother of a child with a genetic condition, the sometimes-harrowing health emergencies she faces, and how she has learned to live with uncertainty.

When Rachel Callander’s daughter Evie was born was born with a rare, chromosomal disorder, she was told she wouldn’t walk, talk, or eat solid food. The doctor said her condition was “incompatible with life.” Callander's own experience of her daughter was quite different. She said Evie made her stronger, taught her to celebrate life more intentionally, and to have a bigger and more open-hearted view of humanity. When Evie died at age two-and-a-half, Callendar, a photographer, traveled across New Zealand to photograph other children with genetic disorders in the Super Power Baby Project, an award-winning book of photography of children with genetic disorders. She has also built on her experience as a new mother to work with doctors and other healthcare professionals to help them become more effective communicators with patients and learn how to use language that empowers, rather than alienates, them. We spoke to Callander about life with Evie, the Super Power Baby Project, and what doctors need to know about talking to patients and their parents.

When Muriel Finkel’s uncle became unable to live alone because of amyloidosis, a rare condition in which misfolded proteins accumulate in organs throughout the body, he moved in with Finkel and her husband. As a caregiver, she struggled to understand his condition and medical needs. After his death in 2003, she co-founded Amyloidosis Support Groups to provide peer group support to patients, caregivers, families, and friends of those touched by the life-threatening disease. We spoke to Finkel about her own experience as a caregiver, what led her to establish the organization, and what she’d like others to understand about the challenges caregivers face.

When Onno Faber began experiencing hearing loss in his left ear four years ago, doctors suspected an infection and prescribed steroids. His hearing loss didn’t slow and after several failed treatments, an MRI revealed a large tumor on a critical nerve. Months later, a second tumor was discovered affecting the nerve for his other ear and he was diagnosed with the rare genetic disease neurofibromatosis type 2. A technology entrepreneur, Faber sought to apply what he learned in his career to fight his disease. He founded RDMD with a mission to accelerate rare disease drug development by creating a platform to make needed patient data available to drug developers. We spoke to Faber about his own rare disease journey, the creation of RDMD, and how his company has evolved.

When Katheryn Elibri Frame’s daughter was diagnosed with CDKL5 disorder, a rare neurological condition that causes treatment-resistant seizures and often severe developmental and cognitive impairments, she co-founded the International Foundation for CDKL5 Research and worked to create a roadmap to a cure. Now, she’s focusing on clinical care and advocacy for CDKL5 patients. We spoke to Frame, president and founder of the CDKL5 Research Collaborative and a Global Genes 2018 Rare Champion of Hope nominee, about the condition, her work as a patient advocate, and her efforts to create centers of excellence to improve clinical care of CDKL5 patients.

As a college student at Syracuse University, Rob Long was an All-American punter bound for the NFL. His plans took an unexpected turn, though, when he was diagnosed with a rare brain cancer during his senior year. Today, Long is director of strategic development for Uplifting Athletes, a nonprofit organization that raises awareness and funding for rare diseases through a network of college student athletes. We spoke to Long about his own rare disease journey, how he became involved with Uplifting Athletes, and the work of the organization.

At the age of 4, Destiny Lamonte was diagnosed with vascular Ehlers-Danlos syndrome, a rare connective tissue disorder and considered the most severe form of EDS. As a result of her condition, Lamonte has contended with a long list of complications and underwent multiple surgeries. Nevertheless, she managed to earn a college degree in psychology and today provides support to people in crisis through an online counseling service. We spoke to Lamonte about her life with a rare condition for which there is no therapy, how she has navigated the complexities of the disease, and how she learned to advocate both for herself and others.

Biobanks play a critical role in biomedical research, providing scientists with ready access to cell lines, DNA, and other biomaterials that can provide insights into the causes and mechanism of diseases. Coriell Institute for Medical Research, one of the world’s leading biobanks, has long served as a steward of important collections of biomaterials for the National Institutes of Health and other organizations. We spoke to Debbie Requesens, co-principal investigator of the National Institute of General Medical Sciences Human Genetic Cell Repository at Coriell, about the role of biobanking, how it can accelerate research into rare genetic diseases, and what patients can do to ensure researchers have access to materials related to their conditions.

Nonsense mutations, genetic mutations that abruptly halt the construction of a specific protein before it is complete, underlies a wide range of rare, genetic diseases. Eloxx Pharmaceuticals is developing therapeutics that address this type of error by restoring production of the complete protein. We spoke to Bob Ward, CEO of Eloxx, about nonsense mutations, the company’s library of small molecule compounds that target the protein production mechanism, and why this approach may offer a way to get at hundreds of rare diseases.

When Daniel de Boer’s son was diagnosed with Cystic Fibrosis, the serial entrepreneur gathered a group of biotech experts to pursue a new approach to treating rare diseases. His company ProQR is developing a platform for correcting faulty RNA that underlie specific rare diseases. We spoke to de Boer about how he came to launch ProQR, the company’s platform technology, and why the approach may be able to address a broad range of diseases.

Joseph Merrick, who was known as the Elephant Man, suffered from Proteus syndrome, a rare disorder that causes abnormal and disproportionate overgrowth of the skeleton, skin, adipose tissue, and central nervous system. ArQule is developing a treatment for Proteus syndrome and other overgrowth disorders. We spoke to Brian Schwartz, chief medical officer of ArQule, about its potential treatment for Proteus syndrome, how it works, and why it may have implications in a number of other indications including several forms of cancer.

BrainStorm Cell Therapeutics is developing autologous stem cell therapies for debilitating neurodegenerative diseases such as ALS. Its platform technology induces mesenchymal stem cells to secrete high levels of neuro-protective factors that promote the survival of neurons. We spoke to Chaim Lebovits, CEO of BrainStorm, about ALS, the company’s platform technology, how the company’s approach may be able to address a range of neurodegenerative diseases.

Dystrophic epidermolysis bullosa is a rare genetic disease that affects the skin and other organs. People with the condition have skin that is so fragile that minor trauma can cause blistering and wounds. It is a painful condition and can have fatal consequences. Krystal Biotech is developing a gene therapy delivered as a topical gel for DEB and other skin conditions. We spoke to Krish Krishnan, CEO of Krystal Biotech, about the company’s gene therapy platform, why it uses the herpes simplex virus as a vector, and how its off-the-shelf gene therapy works.

Lisa Bentley spent 20 years competing as a professional athlete, although early in her career she kept secret that she suffered from the rare lung disease cystic fibrosis. Despite her medical condition, Bentley won 11 Ironman races and 11 half Ironman races, had several top five finishes at the Ironman World Championships, and represented Canada on multiple national teams and at the Pan American Games. We spoke to Bentley about her new book An Unlikely Champion, why she eventually went public about her condition, and why she considers having CF a gift.

Fragile X Syndrome is a rare developmental disorder and the most common cause of inherited intellectual disability. Tetra Discovery Partners, building on research about the role the enzyme PDE4 plays in the disease, is developing an experimental drug to inhibit its activity. We spoke to Mark Gurney, chairman and CEO of Tetra Discovery Partners, about Fragile X, the potential of its PDE4 inhibitor, and why this drug may have therapeutic benefit in a range of neurodegenerative diseases.

The treatment of hemophilia has been moving toward longer periods between the dosing of recombinant factors. Now, with the advent of gene therapies, the potential of a one-time curative treatment appears to be on the horizon. But Catalyst Biosciences believes it can improve care for patients with the rare bleeding disorder with a daily self-injection. We spoke to Nassim Usman, CEO of Catalyst, about the company’s approach to hemophilia, how its drugs work, and why he believes his company’s pipeline may provide better alternatives for hemophilia patients.

Rare cancers, like other rare diseases, face the challenges of mustering research attention, access to patients and biological materials, and generating the interest of drug developers. Nevertheless, as a group, rare cancers are the leading cause of cancer deaths in the United States. The Rare Cancer Research Foundation is seeking to change the research and development landscape in rare cancer by bringing together patient organizations and researchers and building the necessary pieces needed to advance research and the development of therapeutics. We spoke to Barbara Van Hare, Director of Foundation Partnerships at The Rare Cancer Research Foundation, about the rare cancer landscape, how the foundation is forging collaborations between patient groups and researchers, and how its Pattern.org project is developing a crucial source of biological samples to advance research.

In August 2016, Luke Rosen’s two-year old daughter, Susannah, was diagnosed with a rare, neurodegenerative disease called KIF1A Associated Neurological Disorder. At the time, she was one of only about 15 people known to have the condition. Ahead of the upcoming RARE Patient Advocacy Symposium hosted Saturday, May 19 by Global Genes, in partnership with the Penn Medicine Orphan Disease Center at the University of Pennsylvania's Perelman School of Medicine, we spoke to Rosen about his journey as a patient advocate, how he has sought to build an organization to advance research into his daughter’s condition, and his work now as a patient advocate within a biotech company.

For patients with a rare disease, the diagnostic odyssey can be a long journey fraught with many wrong answers. The Undiagnosed Diseases Network is a research study funded by the National Institutes of Health to bring together clinical researchers from across the country armed with advanced technologies to solve the most vexing cases. Ahead of Undiagnosed Disease Day on April 29, we spoke to Kimberly LeBlanc, associate director of research operations for the Undiagnosed Diseases Network, about the challenges rare disease patients face in getting a diagnosis, how the network works, and why its work holds the potential to help clinicians better diagnose rare disease patients.

Before most rare disease patients have a name to give their condition, they go on a diagnostic odyssey than can take years and usually involves multiple specialists. For some patients, the answer never comes. In the absence of a diagnosis, patients face significant challenges getting the care they need, reimbursed by insurers, or necessary accommodations from schools or employers. Ahead of Undiagnosed Disease Day, which takes place April 29, we spoke to Gina Szajnuk, executive director of the Rare and Undiagnosed Network and Matt Might, Director of the Hugh Kaul Personalized Medicine Institute at the University of Alabama at Birmingham School of Medicine. They discussed what it’s like to be undiagnosed, efforts to raise awareness about the plight of undiagnosed patients, and why “undiagnosed” is a diagnosis.

Seth Rotberg grew up in the shadow of Huntington’s disease, a rare, genetic, neurodegenerative condition. Children of people with Huntington’s have a 50 percent chance of developing it themselves. When Rotberg was in college, he made the decision to get tested to see if he too would develop the disease. We spoke to Rotberg about his decision to get tested, why he largely kept the results to himself for two years, and what led him to become a patient advocate.

For people with inherited retinal diseases, gene therapies carry the promise of potentially preventing and even curing blindness. But the small patient populations for with people these conditions make it difficult to attract commercial interests. Odylia Therapeutics, a recently unveiled nonprofit gene therapy developer, is hoping to bridge the gap between academic researchers and drug developers by conducting preclinical and early-stage clinical development on gene therapies for inherited eye diseases. We spoke to Scott Dorfman, co-founder and CEO of Odylia, about what drove the creation of the company, how it works as a nonprofit, and whether it may make sense to extend the model to carry these therapies to patients.

While breakthroughs in the ability to diagnose newborns with genetic diseases continues to expand in scope and fall in cost, the extent of newborn screening varies state-by-state. Nevertheless, the improving affordability of newborn screening is expanding access to these tests for parents seeking them. We spoke to Eric Schadt, CEO of Sema4, about the changing landscape for newborn screening, the company’s Natalis test, and how far off we are from routine screening of newborns with comprehensive genetic sequencing.

Inflammation is a complex biological response to potential threats. But sometimes when the immune system is triggered, its fails to resolve, and unwanted damage ensues. Many inflammatory diseases result from a flooding of signals to activate the immune system without adequate off-signals to resolve it. Corbus Pharmaceuticals lead candidate lenabasum targets the immune system off-switch. The company is in late-stage testing of the experimental therapy for the rare condition systemic sclerosis. We spoke to Yuval Cohen, CEO of Corbus, about the workings of the immune system, what lenabasum does, and why it may have use in a broad number of chronic inflammatory and fibrotic conditions.

Developing therapeutics for rare diseases can be challenging, and not just because of the small patient populations. Often the progression of a disease is not well understood, the patient population can be heterogenous, and the development of objective and meaningful endpoints for a trial can be difficult. We spoke to Ralf Rosskamp, chief medical officer of Dicerna, about how his company has navigated the various challenges in its effort to develop a treatment for a rare liver disorders, how it finds patients, and how it determines endpoints.

Nearly a year ago, more than 400 members of spinal muscular atrophy community along with industry, clinicians, and researchers convened a patient-focused drug development meeting with the U.S. Food and Drug Administration to give voice to patient views on the impact the rare condition has on their lives and their priorities for treatments. CureSMA, which organized the event, recently issued its Voice of the Patient report based on the meeting. We spoke to Rosángel Cruz, associate research director of clinical affairs for CureSMA about the report, how it is being used, and what other patient groups could learn from CureSMA’s experience.

Makayla Allison’s daughter Lily was born with a rare genetic disease with many symptoms, complex challenges, and no diagnosis. As she grew older, one of the things she told her mother she wanted was to have friends like her, ones with the same health issues. That led Allison to create Someone 1 Like You, an online service that connects people with rare diseases with others with the same conditions. We spoke to Allison, founder and CEO of Some 1 Like You, about the genesis of the service, how it works, and why a diagnosis isn’t necessary to finding a connection.

Marfan syndrome is a genetic disorder that affects the body’s connective tissue. Though people with the disease can look long and lean and ideal for certain sports, strenuous activity can be dangerous because the disease can cause enlargement of the aorta and lead to sudden death under extreme exertion. For Marfan Syndrome Awareness Month we spoke to Alan Braverman, professor of medicine at Washington University, cardiologist at Barnes-Jewish Hospital and a member the professional advisory board and board of directors of The Marfan Foundation, about the disease, how it’s diagnosed, and what patients with the condition can do to lead a long and healthy life.

Rare disease centers at academic institutions are usually places that focus on early-stage research of faculty members, but the Orphan Disease Center at the University of Pennsylvania’s Perelman School of Medicine takes a multidimensional approach to address the needs or the rare disease community. In addition to conducting its own research, the center collaborates with both pharmaceutical companies and patient groups, makes grants to support external research, and helps patient groups and families find new researchers and helps guide them to develop essential tools to work on a specific disease. We spoke to Ashley Winslow, senior director of portfolio development at the center, about its work, how it has evolved from its origins, and how it leverages the work it does through collaboration.

World Rare Disease Day is marked on the last day of February by rare disease patient advocates across the globe as a way to raise awareness. This year, the focus of the day will be on research. In recognition of that, we spoke to Anne Pariser, deputy director of the Office of Rare Diseases Research at the National Center for Advancing Translational Sciences. Pariser discussed the changing role of patients in research, efforts to accelerate translational science, and what her office will be doing on World Rare Disease Day.

The Boler-Parseghian Center for Rare and Neglected Diseases at Notre Dame University conducts both basic and translational research. It also provides undergraduate students interested in going on to medical school or biomedical research, exposure to rare disease patients and the issues they face. We spoke to Kasturi Haldar, director of the center, about its work, the scientific case for linking rare and neglected diseases, and its upcoming Rare and Neglected Disease Day Conference.

A range of RNAi therapies are moving through clinical development and toward the market providing the promise of new ways to treat genetic diseases. Dicerna, which has a platform that allows for a unique delivery mechanism for targeting the liver with RNAi therapies, recently began dosing patients in an early-stage trial of its experimental RNAi therapy to treat hyperoxaluria, a rare genetic liver disease. We spoke to Doug Fambrough, president and CEO of Dicerna, about the company’s GalXC platform, what makes it unique, and what’s ahead in its pipeline.

Repurposing, finding new uses for already approved drugs, has long been viewed as a way bring needed therapies to rare disease patients that’s fast and cost-effective. Pharnext is putting a new twist on repurposing by using genomic data and network pharmacology to identify thousands of molecules that may be involved in a disease and finding synergistic combinations of available therapies to treat it. We spoke to Daniel Cohen, CEO of Pharnext, about its so-called Pleotherapy, how it goes about finding and formulating combinations of drugs, and why this may hold greater promise than traditional repurposing approaches.

uniQure achieved a milestone when it won approval in Europe for Glybera, the first gene therapy approved in the Western World, but it later pulled it from the market because it wasn’t commercially viable. Now, it is advancing a gene therapy for the rare genetic clotting disorder hemophilia B through development. We spoke to Steve Zelenkofske, chief medical officer at uniQure, about what the company has learned from its experience with Glybera, what the data from its hemophilia B gene therapy has shown, and how its expecting to alter that therapy to make a more effective version that may provide an even greater response.

PAP and NTM are two rare lung conditions with different pathologies. PAP is an autoimmune condition while NTM is caused by a bacterial infection. Savara Pharmaceuticals is developing an inhaled therapeutic it thinks can treat each of these two different conditions. We spoke to Rob Neville, co-founder and CEO of Savara, about the company, its lead therapeutic Molgradex, and what a recent grant from the Cystic Fibrosis Foundation will mean to advancing another candidate in its pipeline.

The microbiome has become an area of great interest among drug developers as a way to treat diseases. Synlogic, which is developing a new class of therapies it dubs Synthetic Biotics, thinks it may offer novel ways to address a variety of rare diseases. We spoke to Andrew Gengos, chief operating officer and head of corporate development for Synlogic about its platform technology, a recent alliance that may speed the discovery of new therapeutics for the company, and why the microbiome may be a way to address a variety of genetic diseases.

Earlier this month the U.S. Food and Drug Administration issued a draft guidance intended to help cut the cost and development time of rare disease therapies. The guidance focused on the potential to use multi-arm, multi-company trials to reduce the total number of patients needed to evaluate experimental therapeutics targeting the same indication. We spoke to James Valentine, associate with the law firm Hyman, Phelps & McNamara, about the draft guidance, how broadly applicable it might be, and what it says about the direction of the FDA in terms of addressing issues of concern to the rare disease community.

Despite growing acceptance that patients have the clearest view of the health outcomes that matter, drugs to treat rare diseases often live or die on outcome measures that may fail to reflect their benefits to patients. As a result, regulatory approval and reimbursement decisions may made in the absence of measures of meaningful health outcomes for patients. We spoke to Thomas Morel, a research fellow at KU Leuven in Belgium and co-author of an article in the November issue of the Orphanet Journal of Rare Diseases, about the particular challenges of rare disease clinical trials, the importance of patient-centered outcome measures for them, and what it will take to develop and use such measures for rare disease clinical studies.

Earlier this month, the U.S. Food and Drug Administration announced a comprehensive policy framework for the development and oversight of regenerative medicine products. The framework spells out how the FDA intends to review new products and protect patient safety in this emerging area that FDA Commissioner Scott Gottlieb called “dynamic and complex” with “unique challenges.” We spoke to Michael Werner, executive director of the Alliance for Regenerative Medicine, about the framework, whether it provides the clarity industry sought, and what it will mean for patients hoping to see safe and effective regenerative therapies reach them as quickly as possible.

The pricing of drugs is characterized by a tension between providing incentives to drug companies to invest in the development of innovative therapies and ensuring affordability so patients have access to needed medicines. The Institute for Clinical and Economic Review, an independent non-profit research institute that analyzes the evidence on the effectiveness and value of drugs and other medical services, recently issued final modifications to its framework for assessing the value of treatments for serious, ultra-rare diseases. The framework applies to therapies that are eligible to treat no more than 10,000 U.S. patients including certain treatments for inherited eye disease, hemophilia A, and cystic fibrosis. We spoke to Steven Pearson, president of ICER, about the framework, why modifications were needed for drugs to treat ultra-rare diseases, and what the implications are for a pipeline or therapies with the potential not just to treat, but to cure progressive and deadly rare diseases.

Stories abound about plucky entrepreneurs financing their startups, but it’s unusual to get trench-view insights from founders who have slogged their way through endless pitches along Sand Hill Road. Ethan Perlstein, founder and CEO of the rare disease drug discovery company Perlara, shared what he gleaned from his recent $7.4 million equity round for his company in a piece on the CNBC website. We spoke to Perlstein about his experience, what he learned in the process, and his practical advice for entrepreneurs seeking funding.

Health Canada has derailed a long-fought effort to establish a framework for orphan drugs. Last month the agency, without warning, removed from its website all documents relating to the effort. The agency says its conducting a broader review of regulations and will now seek to address the aims of the orphan drug framework through other means. The decision is a blow to rare disease advocates in Canada, who view the move as a response to provincial governments who feared an orphan drug designation would be a license to charge high prices for medications. We spoke Durhane Wong-Rieger, president and CEO of The Canadian Organization for Rare Disorders, about the Health Canada’s unexpected decision, why an orphan drug framework is seen as critical to making needed therapies available in Canada, and what it means for the rare patient community there.

Cydan, an orphan drug accelerator focused on developing therapies for rare genetic diseases, recently completed a $34 million financing round. With a core team that seeks to in-license promising experimental therapies, Cydan conducts preclinical development in-house and then, should circumstances warrant, spins out a company to conduct clinical development of promising assets. It’s first company Vtesse, which is developing drug for Niemann-Pick Disease Type C, has already been acquired. Its second company, Imara, is developing a treatment for sickle cell disease. We spoke to Chris Adams, CEO of Cydan, about its business model, how it differs from other similar approaches, and whether it provides a faster and cheaper way to get therapies to market.

Rare disease caregivers are good at advocating for their family members, for research, and for the needs of rare disease patients broadly. What they often fail to do, though, is advocate for themselves. The National Alliance for Caregiving, in partnership with Global Genes, is conducting a first-of-its-kind study of rare disease caregivers to better understand the challenges they face and determine whether there are common issues they share that may warrant policy changes. We spoke to Grace Whiting, Interim CEO and Chief Operating Officer of the National Alliance for Caregiving, about the study, what the organizations are hoping to determine, and how the findings will be used.

Prometic Life Sciences is developing both plasma-derived and small molecule therapeutics to address a number of rare diseases that are today without therapies. Its lead experimental therapeutic is Ryplazim, which is purified human plasminogen that is being developed to treat congenital plasminogen deficiency. Plasminogen is a naturally occurring protein that plays a critical role in wound healing, cell migration, tissue remodeling, angiogenesis and embryogenesis. We spoke to Pierre Laurin, president and CEO of Prometic, about Ryplazim, the challenges and benefits of deriving products from human plasma, and what else is moving through the company’s pipeline.

Claire Wineland has defied the odds. At 20, she’s lived more than twice as long as doctors told her parents she would. Born with cystic fibrosis, Wineland has spent about a quarter of her life in hospitals, and her daily health regimen is a demanding routine of treatments, medications, and oxygen. Despite her health problems, though, she has learned to find purpose by helping others. At the age of 13 she founded Claire’s Place Foundation to provide support to CF patients and their families. She’s also touched many others with her YouTube videos and public talks where she speaks about her illness and dying, with charm, humor, and a life-affirming wisdom. We spoke to Wineland, a 2017 Global Genes’ Champion of Hope awardee, about her life with cystic fibrosis, what its taught her about living, and how finding a greater purpose than treating her own illness transformed her life.

When Amber Olsen’s daughter Willow was diagnosed in 2016 with an ultra-rare lysosomal storage disorder known as multiple sulfatase deficiency, the diagnosis was grim. There is no treatment for the disease and most children with the condition don’t live past the age of 10. Unlike other lysosomal storage disorders that have been treated with enzyme replacement therapies, MSD involves a lack of multiple enzymes. It also includes significant central nervous system involvement that makes delivery of therapies that much more challenging. We spoke to Olsen about MSD, the United MSD Foundation she founded to drive research toward treatments, and how she enlisted one researcher to pursue a potential gene therapy.

Disorder: The Rare Disease Film Festival will debut in Boston October 2 and 3 featuring a range of more than 30 films focused on topics of rare disease. The event will also include talks from filmmakers, patient advocates, and researchers as the organizers not only hopes to raise awareness about rare diseases, but also begin conversations and forge connections. We spoke to Bo Bigelow, one of the organizers of the event, about the film festival, his own search for answers about his daughter’s ultrarare condition, and why this festival is about more than just the films themselves.

People with a chronic illness may be able to work, but commuting to a 9-to-5 job in an office might not be ideal. Chronically Employed (http://chronicallyemployed.com/) is a new website that offers job listings, career advice, and stories for people who continue in their careers after a diagnosis. We spoke to Ilana Jacqueline, editor-in-chief of Chronically Employed, about the new site, the changing view of employers toward work-at-home employees, and the growing opportunities for jobseekers with a chronic illness.

Partnering is essential to advancing rare disease therapies, but while researchers, drugmakers, and patient groups share a common desire to bring new treatments to market, differences in how they operate, their culture, and priorities can derail progress. We spoke to Karen Erickson, associate executive director of community engagement at the Alpha-1 Foundation, about the elements of successful partnering, how to align the differing interests of the participants, and how to get everyone to work together to achieve common goals.

Art Pappas, a former pharmaceutical executive turned venture capitalist, has spent more than 30 years working for and investing in drug companies. Among the areas he focuses on are rare disease drug developers. We spoke to Pappas about the changing climate for investment in rare disease companies, his thought process in evaluating potential investments, and at what point he considers exit strategies.

Patient organizations have long been working with biopharmaceutical companies, but as they have grown more sophisticated about their interactions, they are coming to understand the value in laying out the ground rules for these relationships. Last year, the International Fibrodysplasia Ossificans Progressiva Association, or IFOPA, took the unusual step to craft a set of guidelines for the organization regarding how it engages with the pharmaceutical industry. It made these guidelines public and continues to refine them. We spoke to Betsy Bogard, chair of the IFOPA research committee, about why the organization created the guidelines, how they have affected interactions between the organization and industry, and how other organizations are interested in following suit.

To bring new therapies to market to treat rare diseases requires more than scientific innovation. Innovation in financing and business models can be critical as well as the need to find ways to cost effectively develop new medicines becomes increasingly important. We spoke to Neil Kumar, CEO of BridgeBio, about his company’s strategy for developing a portfolio of rare disease therapeutics, why the company’s not alone in this effort, and what he’s learned so far through this approach.

A group of twentysomethings backpacking their way through Europe may not sound unusual, but for Kevan Chandler and his friends, their trip in 2016 was by no means a typical backpacking adventure. Chandler, born with the rare neuromuscular condition spinal muscular atrophy, has been wheelchair bound for most of his life. Because the planned trip included several places that were not wheelchair accessible, the friends decided to rig a backpack to carry Chandler and leave the wheelchair at home. We spoke to Chandler about the journey, how it led to the creation of the nonprofit We Carry Kevan, and why he is working to change the way people think about accessibility and dependency.

Simon Wheatcroft lost his ability to see at the age of 17, the result of a rare genetic disorder. After becoming blind, though, Wheatcroft developed a penchant for running. Starting on a soccer field where he ran between goal posts, he graduated to public roadways. Since those early outings where he had sometime painful encounters road signs and other obstacles, Wheatcroft has learned to adapt, use technology and his other senses, and become an ultramarathoner. We spoke to Wheatcroft about the loss of his sight, how he has been able to adapt, and what he’s learned about himself in the process.

Last month, Spark Therapeutics submitted its gene therapy Luxturna, an experimental treatment for a rare inherited disease that causes blindness, to regulators in the United States and Europe. The company also won U.S. Food and Drug Administration designation for the experimental therapy as a treatment for a rare pediatric disease. Luxturna could be the first treatment for inherited retinal disease and the first gene therapy for a genetic disease approved in the United States. We spoke to Paulo Falabella, medical affairs ophthalmic lead for Spark Therapeutics, about Luxturna, what clinical trials to date tell us, and why this represents a significant development for not just Spark, but the entire field of gene therapy.

Fulcrum Therapeutics is working to develop small molecule drugs to modulate gene activity as a way to treat certain rare diseases. The company, established by the venture capital firm Third Rock Ventures, is initially focusing on Fragile X and a form of muscular dystrophy known as FSHD. We spoke to Walt Kowtoniuk, director of strategy and operations for Fulcrum, about its approach, what he learned working in a venture capital firm, and what advice he would offer rare disease patients turned investors.

When BioMarin failed to win U.S. Food and Drug Administration approval for its experimental Duchenne muscular dystrophy drug drisapersen, it decided to its cease development. Though there were concerns about both the safety and efficacy of the drug, there were patients who participated in the clinical trials who felt that they benefitted from it. CureDuchenne established CD Access, a new nonprofit that negotiated a novel agreement with BioMarin to get control of the existing supply of drisapersen, which the nonprofit is distributing to patients in Canada who participated in the clinical trials. We spoke to Debra Miller, CEO and founder of CureDuchenne and CD Access, about the program, how it works, and whether it serves as a model for getting other similar drugs to patients in the future.

The diagnostic odyssey rare disease patient face can be long and daunting. Centogene is trying to help these patients find answer more quickly through its genetic diagnostics. The company has been focused on getting beyond the noise generated by the rapid increase in the volume of data to get accurate understanding of a patient’s genetics and helping doctors obtain actionable information. Strengthened with a recent $28 million financing, the company is expanding its presence in the United States. We spoke to Arndt Rolfs, CEO of Centogene, about the company’s genetic diagnostic services, its expansion plans, and the competitive advantage it believes it holds in its proprietary data.

PFIC is a rare genetic disorder that causes progressive, life-threatening liver disease. In many cases, PFIC leads to cirrhosis and liver failure within the first 10 years of life. Albireo, a 2008 spin-out of AstraZeneca, is developing bile acid modulators to treat PFIC and other rare pediatric liver diseases and gastrointestinal disorders. We spoke to Ron Cooper, CEO of Albireo, about PFIC, the challenge of developing a therapy for a disease with multiple forms and causes, and the path forward for the company.

aTyr Pharma is exploring a new set of naturally occurring proteins within the body dubbed physiocrines that modulate biologic activity and may provide therapeutic benefit. The company is pursuing this new class of molecules to treat a number of rare diseases. The company’s lead drug candidate Resolaris is being developed to treat FSHD, a rare genetic myopathy in which immune cells invade diseased skeletal muscle and cause muscles to grow weak and deteriorate. We spoke to John Mendlein, CEO of Atyr Pharma, about physicorines, how they can restore homeostasis to the immune and other systems, and why these molecules might be harnessed to treat a range of diseases.

Duchenne Muscular Dystrophy, a rare genetic disease, causes progressive muscle wasting that slowly robs people of abilities and leads to death. In recent years, much attention has focused on the use of antisense oligonucleotides to bypass defective portions of the exon that codes for the dystrophin gene to restore its production. Dystrophin is a protein that is essential to healthy muscle. Summit Therapeutics is taking a different approach. Instead of restoring dystrophin, Summit is developing a drug that activate utrophin, a related protein that serves a similar function to dystrophin during fetal development, but then shuts off. We spoke to Glyn Edwards, CEO of Summit, about the company’s utrophin activator ezutromid, its licensing deal with Sarepta Therapeutics, and why, unlike the exon-skipping drugs that target specific subpopulaitons of Duchenne patients, ezutromid could provide benefits to patients broadly.

Enzyme replacement therapies are available for a number rare, metabolic diseases that collectively are known as lysosomal storage disorders. These therapies have brought great benefits to patients. One problem, though, is that the enzymes don’t cross the blood-brain barrier and don’t address the severe and progressive neurological complications caused by many of these diseases. ArmaGen thinks it has a solution. By connecting the enzyme to a protein that is allowed to cross the blood-brain barrier, ArmaGen hopes to exploit a natural mechanism to address the CNS complications of these diseases. We spoke to Mathias Schmidt, CEO of ArmaGen, about the company’s platform technology, its pipeline of enzyme replacement therapies for lysosomal storage disorders, and its implications for more common neurological diseases.

The promise of gene editing and gene therapy has rare disease patients not only contemplating the potential of new treatments, but ones that can free them from chronic therapies and potentially provide cures. Sangamo Therapeutics, long pursuing its proprietary gene editing technology, is suddenly moving into the clinic with four experimental therapies including a a gene therapy for hemophilia A, and gene editing therapies for hemophilia B, MPS I, and MPS II. The company is currently enrolling three trials and expects to begin enrollment on a fourth trial later this month. We spoke to Sandy Macrae, president and CEO of Sangamo, about the diseases it is targeting, the company’s unique approach to gene editing, and it strategy for moving its therapies through clinical development and to the market.

Clinical trials for rare disease therapies face many challenges due to the small patient population on which they draw, the fact that often there may be many unanswered questions about a specific disease, and the potential variation in the way a rare disease manifests itself in patients. We spoke to John Boland, vice president of product development for the Atlantic Research Group, about the contract research organization’s recent white paper on “Critical Considerations for Rare and Orphan Disease Trial Planning” (http://bit.ly/2qE2qpb), the special challenges of conducting rare disease clinical trials, and how to best address these unique challenges.

For many rare disease patients, the drug discovery and development process moves slower than the diseases they are battling. Earlier this month, representatives of the patient community joined with academic researchers and drug developers at the Charles River Rare Disease Symposium in Cambridge, Massachusetts to explore way to accelerate the process of drug discovery and move more quickly toward human clinical trials. We spoke to Doug Macdonald, director of research operations and scientific alliances for CHDI Management and Antti Nurmi, managing director of Charles River Discovery Services, about the obstacles to rare disease drug discovery, the critical role collaborations play, and what can be done to accelerate the process.

Last month the U.S. Food and Drug Administration granted Enzyvant both Breakthrough Therapy Designation and the newly established Regenerative Medicine Advanced Therapy Designation for its investigational cell therapy to treat complete DiGeorge Syndrome, a rare and fatal disease. Enzyvant is the first company to win both designations and only the second to win the Regenerative Medicine Advanced Therapy Designation established through the 21st Century Cures Act. The designations provide for accelerated review pathways and special access to developmental guidance from the FDA. We spoke to Alvin Shih, CEO of Enzyvant and Louise Markert, the Duke University immunologist who has been pioneering the therapy, about Complete DiGeorge Syndrome, the innovative approach they are using to treat it, and the path forward for the therapy. As a matter of disclosure, Shih is co-chair of Global Genes Medical and Scientific Advisory Board.

There is increasing recognition of the important role patients can play by providing their insights into the drug discovery and development process. The Penn Medicine Orphan Disease Center and Global Genes will be hosting the second annual Rare Patient Advocacy Symposium in Philadelphia May 19, at the Sheraton University City Hotel, a day-long exploration of how rare disease patients can better get their voices heard in this process. We spoke to David Fajgenbaum, associate director of patient impact for the Penn Medicine Orphan Disease Center and research assistant professor of Medicine at the Perelman School of Medicine, about the changing view of rare disease patients, their emerging role in the drug development process, and the value they can provide to researchers, regulators, and drug developers.

Porphyria is a rare and intensely painful blood disease. Because it can manifest itself with symptoms similar to those caused by far more common disorders, it can be difficult to diagnose. Colin McEwen went through an 18-year diagnostic odyssey, in part because injuries he suffered as a child from an auto accident obscured from doctors the actual cause of his maladies. His problems were made that much more difficult as his search for relief from the pain from his disease led doctors to dismiss him as a drug-seeker. We spoke to McEwen about porphyria, the experiences he went through to get to a diagnosis, and how having a diagnosis has changed his ability to manage the disease.

Diagnosing a rare disease can take years. When it’s a disease that’s never been identified before, the search for a diagnosis can be that much more difficult. Daryl Scott, associate professor of molecular and human genetics at Baylor College of Medicine, and colleagues diagnosed four patients on two continents with a never before identified rare disease in a day. The feat is recounted in a recent study published in the journal PLoS ONE (http://bit.ly/2oEXhy5). We spoke to Scott about the diagnosis, how it all came together, and what it says about the role of data and collaboration in medical detective work today.

Researchers at UCLA have developed a stem cell gene therapy treatment for children born with the rare, life-threatening condition ADA-deficient SCID, often referred to as Bubble Baby disease. Children born with this condition are without a functioning immune system and are kept in controlled and isolated environments because exposure to common illnesses or infections can be lethal. We spoke to the treatment’s developer Donald Kohn of the UCLA Eli and Edythe Broad Center of Regenerative Medicine about the stem cell gene therapy, the promising results he’s had restoring normal immune function in clinical trial patients, and why this approach holds promise in other rare conditions.

Legislation that would provide incentives to drugmakers to repurpose existing pharmaceuticals as rare disease treatments is once again in the works. Known as The OPEN ACT (Orphan Product Extensions Now, Accelerating Cures and Treatments), proponents say it would help address a gap in the drug development landscape. At one point, the bill had been folded into the 21st Century Cures Act, but had been stripped out before passage. We spoke to Max Bronstein, chief advocacy and science policy officer for the Everylife Foundation for Rare Diseases, about the legislation, why its needed, and what it will take to get passed.

The high cost of drug development and the small populations for individual rare diseases can make it difficult to attract drug companies to make the investment of time, money, and resources necessary to bring a rare disease drug to market. American MedChem, a non-profit drug company, is hoping to bridge a gap between the lab and the clinic, by using its small molecule expertise to advance potential rare disease therapies to a point where a drug company might seek to license them. We spoke to Robert Selliah, founder, president, and CEO of American MedChem, about its business model, what a non-profit can do that a for-profit pharmaceutical company can’t, and how it is prioritizing the projects it is pursuing.

Rare disease advocates, because of their diseases’ small population of patients, can find it challenging to muster the interest of researchers and drug developers to invest the money, time, and energy needed to discover and develop a therapeutic. One solution is to drive collaborations to leverage the limited resources of foundations and researchers and advance their efforts to a point where drug company may be willing to take over development. Support of Accelerated Research for Niemann-Pick C, or SOAR-NPC, represents such a model. We spoke to Cristin Davidson, a researchers and project manager for SOAR-NPC, about the organization’s approach, how its tackled various preclinical challenges common to rare diseases, and why the success it has enjoyed should be replicated by others.

Hallie Bae Barnard is an eight-year-old girl with Diamond Blackfan Anemia, a rare condition that has set her family and friends on a search for a suitable bone marrow donor. But her understanding of the need of others in a similar situation has her on a quest to find not only a match for herself, but for many others who are unable to find a life-saving bone marrow donation they need. We spoke to Jennifer Scott, a founding board member and vice president of Media and Communications for Hallie’s Heroes, about Diamond Blackfan Anemia, the challenges of finding bone marrow donors, and the impact the organization is having.

When Milo Lorentzen was born, concerns over his condition sent him to a neonatal intensive care unit where he spent the first ten days of his life. It began a medical and diagnostic odyssey for him and his parents. After six surgeries and undiagnosed global developmental delays, doctors identified a de novo gene mutation to his KDM1A/LSD1 gene that is believed to be the cause of his condition. His parents eventually launched the website Milo’s Journey to tell his story in the hopes of finding others with the same mutation. We spoke to Karen Park, Milo’s mother, about her family’s experience, the challenge of having a child with an ultra-rare disease of unknown consequence, and the experience of finding others with the same condition.

Edgar Kline Jr.’s family can trace its involvement with a rare genetic disease back to the 1700s. In fact, Hagerstown, Maryland, where his family settled, has a higher incidence of hereditary ATTR amyloidosis because of this common ancestor some in the town share. The disease which begins to manifest itself in middle age, can cause damage to the heart, nerves, and various organs. We spoke to Kline about the disease, the difficulty in getting an accurate diagnosis, and why he’s trying to raise awareness about it.

The Internet has opened up a world of information to rare disease patients, but it can often be hard to access, understand, or evaluate. Raremark is working to keep rare disease patients up to date with the latest information about their conditions through its online community built around disease channels. We spoke to Raremark founder Julie Walters about the website, how it curates information, and how its ultimately seeking to empower rare disease patients to make better decisions about their own care.

The translation of a drug from discovery to development faces a number of obstacles, but these can be amplified for rare disease therapies in part because of the smaller populations, heterogeneous nature, and often poorly understood development of a disease. The Catalyst program at the Clinical & Translational Science Institute at the University of California, San Francisco will be holding a one-day symposium on March 3 with leading researchers, drug developers, and patient advocates about the translational challenges rare disease therapies face and how to address them. We spoke to Cathy Tralau-Stewart, interim director of UCSF's Catalyst Program, about the upcoming symposium, the unique translational challenges rare disease therapies face, and what can be done to overcome them. To view the symposium agenda or to register, you can paste this URL (http://bit.ly/2lWmYbB) into your browser.

World Rare Disease Day, an annual international effort to create awareness for rare diseases, will take place February 28. This year, the theme is on how research brings hope to people living with rare diseases. This seemed like an opportune time to talk to Kenneth Hobby, president of CureSMA, about his organization’s efforts to drive research for spinal muscular atrophy, the most common genetic cause of death for infants. We spoke to Hobby about CureSMA’s strategy for research, the role the group played in helping to make possible the first approved therapy for the disease at the end of last year, and what other rare disease organizations can learn from its experience.

Last month, Children's National Health System, the world’s largest provider of care for children with rare genetic disorders, announced the formation of Children’s National Rare Disease Institute. Billed as a first-of-its-kind center focused exclusively on advancing the care and treatment of children and adults with rare genetic diseases, the National Organization for Rare Disorders has designated it as its first Center of Excellence of Clinical Care for Rare Diseases. We spoke to Marshall Summar, chief of Genetics and Metabolism at Children’s National and chairman of NORD, about the new institute, the ambitious vision for it, and the role it hopes to play in transforming care for people with rare diseases.

A group of rare, genetic, metabolic diseases known as lysosomal storage disorders are largely without treatments. Mark Noble believes one way of accelerating the development of therapies for this group of disorders is to look at them collectively instead of individually, and see whether existing drugs might serve as treatments. Noble, professor of Genetics and of Neurobiology and Anatomy at the University of Rochester Medical Center, recently co-authored a study in PLoS Biology (http://bit.ly/2kPbUzJ) that suggests repurposed drugs could address a common aspect of these diseases and provide therapeutic benefit. We spoke to Noble about his research, the findings of this common link in this group of diseases, and the potential implications for using already approved drugs to bring needed treatments to patients.

Sobi is a drugmaker focused on hemophilia, inflammation, and genetic and metabolic diseases. It is now pursuing its drug Orfadin, used to treat the metabolic disorder tyrosemia type 1, as a potential treatment for the metabolic condition alkaptonuria. It is also pursuing Kineret, its drug for the rare inflammatory condition NOMID, as a potential therapy for Still’s disease. We spoke to Rami Levin, president of North America for Sobi, and Len Walt, vice president and head of medical affairs of North America for Sobi, about the company’s evolution, its growing pipeline, and its effort to expand indications for its rare disease drugs.

The large number of rare diseases and the small number of patients afflicted with any one of them can help fuel a sense of isolation these patients feel. Sandra Shpilberg, CEO of Seeker Health, has interviewed many rare disease patients over time as part of her work to help drugmakers find participants for clinical trials. In a recent article on her website she argues that rare disease patients, regardless of their particular ailment, share much in common. We spoke to Shpilberg about the disease burden that rare disease patients face, how they may seek to address some of these issues, and why collaboration throughout the rare disease community is critical to creating better outcomes.

The search for a diagnosis can be a long and difficult journey for patients with a rare disease, but CrowdMed is offering a different way for them to find the answers they seek. The web-based service allows patients to tap a multidisciplinary team of experts to help them solve their medical mysteries. We spoke to Jared Heyman, founder and CEO of CrowdMed about the service, how his the experience his sister faced in getting a diagnosis for a rare disease led to its creation, and why the company, even though its backed by top-flight investors, is now turning to crowdfunding to raise capital.

Collaborations have become a critical aspect of the search for new treatments for rare diseases as drug companies, universities, research institutes, and patient groups are forging alliances to leverage their strengths. Outside this year’s J.P. Morgan Healthcare Conference, Global Genes will convene Rare in the Square in San Francisco’s Union Square to provide rare-disease focused companies and organizations a place to network at the heart of the week’s activities. We spoke to Michael Pistone, director of marketing, innovation & commercialization at Cincinnati Children’s Hospital Medical Center, about his hospital’s rare disease partnerships with drug companies, how the face of partnering in the rare disease space is evolving, and what he’s hoping for at this year’s Rare in the Square event.

Obsessive compulsive disorder, tics, anxiety, attention deficit hyperactivity disorder, and behaviors associated with autism spectrum disorders can be caused by a treatable autoimmune condition that is triggered by common infections. These conditions, known as PANDAS and PANS can often be misdiagnosed and wrongly treated to the detriment of the children with the condition. We spoke to Craig Shimasaki, CEO of Moleculera Labs, which has developed a diagnostic to determine if an individual’s neurologic or psychiatric symptoms could be caused by an autoimmune dysfunction. Shimasaki discussed these conditions, what we know about them, and how the availability of a diagnostic is helping change the way these patients are understood and treated. This is an encore presentation of an interview that first aired in April 2016.

For rare disease patients and their families, genome and exome sequencing may identify mutations that may be drivers of a condition, but nothing more. As families search for a name to put to a disease and look for treatments, finding others with the same condition and researchers working to understand and treat it becomes a critical part of the search for answers. Now researchers at the University of Washington have created MyGene2, a web portal for people with rare genetic mutations to connect with others with the same condition and researchers interested in their particular mutation. We spoke to Michael Bamshad, professor and chief of the Division of Genetic Medicine in the Department of Pediatrics at the University of Washington & Seattle Children’s Hospital, and Jessica Chong, one of the leads on the MyGene2 project at the Center for Mendelian Genomics at the University of Washington, about the portal, how it works, and what they are hoping to accomplish. This is an encore of an interview that first aired April 2016.

When Matt Wilsey daughter Grace was diagnosed with the ultra rare disease NGLY1 deficiency, he travelled the world to get a diverse group of researchers to work on finding answers. His approach to driving research, he says, comes from his experience as a Silicon Valley entrepreneur. We spoke to Wilsey about the experience getting a diagnosis for his daughter, what he learned from others who had gone before him, and the importance of open collaboration across institutions.

The dating world can be difficult to navigate for most people, but for a woman with a variety of rare diseases, the dating world poses additional challenges. Chelsea Freund, author of The Sick and the Dating blog (thesickandthedating.com), chronicles her experiences looking for love while contending with both diagnosed and undiagnosed conditions. We spoke to Freund about her blog, the experiences she’s shared, and the advice she has for others in similar circumstances. This is an encore episode first aired in December 2015.

The Internet giant Google has set its sights on revolutionizing how researchers store, analyze, and share genomic data. The company recently entered into an agreement with the Broad Institute that allows it to integrate Broad’s Genomic Analysis Toolkit into Google Genomics. We spoke to David Glazer, director of engineering for Google, about its Google Genomics platform, the opportunity it sees in genomics, and what it’s doing to help researchers turn vast amounts of data into actionable information. This interview originally aired August 2015.

People often focus on the large amounts of money it takes to conduct biomedical research or develop potential therapeutics, but sometime small grants can have big impacts on the lives of people with rare diseases. Caroline Harding, CEO of Genetic Disorders UK, discusses her own journey through the rare diseases world following the birth of her son Columbus, and how she saw, through her own work, the important role small grant making could play. We spoke to Harding about her experiences, her organization’s Jeans for Genes program, and how small grants can sometimes be the catalyst to transform the lives of people. This is an encore presentation of an interview with Harding that originally aired in November 2015.

David Pearce created the Coordination of Rare Diseases at Sanford or CoRDS registry as a national resource that could help accelerate research into rare diseases. We spoke to Pearce, president of Sanford Research, director of Sanford Children’s Health Research Center, and the Global Genes 2012 Champions of Hope honoree for Research & Science, about his own research into the neurodegenerative disorder Batten Disease, how that led to the development of CoRDS, and the role patient registries can play in accelerating rare disease research and the development of new therapies. This is an encore presentation of an interview with Pearce that originally aired April 2015.

When a doctor delivered a devastating diagnosis to Pat Furlong for her two sons with Duchenne Muscular Dystrophy, she refused to sit by and just watch them slowly die. She marched off to Washington to corner her Senator and the director of the National Institutes of Health, borrowed money to fund her sudden role as a patient advocate, and brought together academic researchers to get them thinking on how they could tackle the disease. We spoke to Furlong, founding president and CEO of Parent Project Muscular Dystrophy, about her experiences, what patient advocates can do to raise awareness for their causes, and how they should think about best leveraging their investments. This is an encore presentation of our April 2015 interview with Furlong.

Harnessing the power of computers to diagnose rare, genetic diseases is not new idea, but Dekel Gelbman is using Big Data to analyze a patient’s phenotype as a clue to his or her genotype. His company FDNA has developed Face2Gene, a platform for analyzing an image of a patient’s face to help arrive at a diagnosis. We spoke to Gelbman about the challenges of diagnosing a rare disease, how Face2Gene works, and why it could accelerate the process of getting a diagnosis.

Drug discovery in the rare disease space is increasingly reliant on collaborations between patient groups, industry, and academia. Charles River Laboratories, the global contract research organization, recently held a symposium in New York City on the need for successful collaborations to advance rare disease drug discovery. Following the symposium we spoke to Patrick Sweeney, managing director of discovery sciences at Charles River, about the evolving nature of rare disease collaborations, how that’s changing the way researchers work, and why Charles River believes it can play a unique role in facilitating rare disease collaborations.

Gene therapy has the promise of radically changing the landscape for rare disease patients without therapeutic options today. Abeona Therapeutics, which is building a pipeline of gene therapies, is not timid in its targets, which includes the progressive neurodegenerative disorders Sanfilippo syndrome types A and B as well as Batten disease. We spoke to Tim Miller, CEO of Abeona, about gene therapy, the company’s pipeline, and the challenges of delivering these therapies to where they are needed within the body.

Rare disease patients are exerting an increasing influence on every aspect of the healthcare continuum and this includes the area of academic research. The Stanford Medicine X conference, held last month, is billed as “an academic conference for everyone.” We spoke to Emma Rooney, patient advocate, storyteller, and 2016 Med X ePatient delegate, about her experience at Med X, her discussions with other rare disease patients there, and the experience rare disease patients have going from children to adults with a rare disease.

Having a rare disease with visible manifestations can cause people to stare or give second looks. Peter Dankelson, a 16-year-old with Goldenhar Syndrome, knows what that’s like. Dankelson, talks to students around the country about his experience of living with a craniofacial condition and uses it to remind students that we are all different. His message is simple. He encourages students to treat others with kindness. We spoke to Dankelson about his works as a teen rare disease advocate, the message he carries to students, and what he’ll be doing October 10 for Choose Kind Day.

The controversial approval of Sarepta Therapeutics eteplirsen to treat a certain form of Duchenne muscular dystrophy has been viewed as a major victory for patient advocates. Advocates aggressively lobbied the U.S. Food and Drug Administration to grant approval for the drug despite a weak data package presented by the company. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research overrode staff to greenlight the drug. We spoke to Debra Miller, president, CEO, and co-founder of CureDuchenne, about the significance of the approval, her organization’s venture philanthropy model, and what other hope the Duchenne drug pipeline may hold for patients.

As databases containing the genetic information of individuals proliferate, an opportunity for physicians, researchers, and individual to find people with specific rare mutations exists. Matchmaker Exchange represents an effort to tie together a variety of databases and make them accessible through a single portal. We spoke to Anthony Philippakis, cardiologist at Brigham and Women’s Hospital and a data scientist at the Broad Institute’s Program for Medical and Population Genetics, about the Matchmaker Exchange, which he helped create. Philippakis discussed how the exchange works, the benefits he hopes it will provide, and the technical and other challenges it faces.

Hereditary angioedema is a rare genetic disease that causes episodes of severe swelling. The swelling can occur in the limbs, face, intestinal tract and elsewhere. Sometimes, it can be life threatening if the swelling obstructs breathing. Though there are limited therapeutic options available, a class of drugs known as RNA interference is offering hope. We spoke to Marc Riedl, professor of medicine and clinical director of the US HAEA Angiodema Center at the University of California, San Diego, about hereditary angioedema, how RNA interference therapies work, and why this may be an area of promise for this and other rare diseases.

Peroxisomal disorders are a group of rare and heterogeneous metabolic diseases. Earlier this year, the National Organization for Rare Disorders selected the Global Foundation for Peroxisomal Disorders as one of 20 rare disease groups to undertake a natural history study with support from the U.S. Food and Drug Administration. We spoke to Melissa Bryce Gamble, president and co-founder of the Global Foundation for Peroxisomal Disorders, about the natural history study, why such studies are critical for expanding the understanding of a rare disease, and how they help inform the development of therapies.

The improved ability to generate and capture data is providing researchers with the potential for new insights into diseases, but the growing volume and complexity of the data has made it difficult to translate all of this into actionable information. We spoke to Spyros Mousses, founder and president of Systems Imagination, about the what the emerging world of Big Data means for rare disease patients, how it requires new ways of approaching scientific problems, and why innovative collaborations are becoming more important than ever to develop new therapies.

The genomic revolution promises to unlock the underlying mechanism of many rare diseases and disorders, but progress in translating new discoveries into therapies that benefit patients can be frustratingly slow. We spoke to Robert Ring, former chief scientific officer of Autism Speaks, about innovative efforts he’s been involved with to overcome bottlenecks in translational medicine, advance research, and attract investment into drug development.

The International Fibrodysplasia Ossificans Progressiva Association focuses on a rare genetic disorder, but it has had great success in stimulating research, engaging with industry, and helping advance needed therapies. We spoke to Betsy Bogard, global research development director for the IFOPA, about FOP, how her organization has helped drive work toward new treatments, and what it’s learned about how to best work with industry partners.

Two years ago, the ALS Association’s Ice Bucket Challenge became a viral sensation on the Internet and raised $115 million to fight the progressive neurodegenerative disease. Now those doused donors are seeing concrete results from the money they gave. A recent paper in Nature Genetics reported on the identification of a new gene that is a contributor to ALS, a finding that was funding in part from Ice Bucket Challenge money and could lead to new therapies. We spoke to Lucie Bruijn, chief scientist of the ALS Association, about the findings, their significance, and lessons for other disease groups seeking to accelerate research.

A widely used drug to treat diabetes may hold promise as a therapeutic for patients with Maple Syrup Urine Disease, a rare, inherited metabolic disorder involving the dysfunction of an enzyme needed to break down three essential amino acids. The findings, which appear in a new study in Nature Scientific Reports come from researchers at the Buck Institute for Research on Aging. We spoke to Arvind Ramanathan, senior author of the study and a member of the Buck faculty, about the study, what it says about the ability to understand more common diseases through the study of rare diseases, and how repurposing existing therapies holds promise of brining new treatments to rare disease patients who are without them.

Expanded access—a means by which physicians and patients can obtain experimental drugs outside of a clinical trial—has been an area of growing interest among rare disease patients. Jess Rabourn, co-founder and managing director of WideTrial, in a new white paper addresses some common misconceptions about expanded access and argues for a new model that aligns charitable, scientific and medical interests for wider patient engagement. We spoke to Rabourn about the evolution of the concept of expanded access, why commercial viability and not the FDA has been the biggest obstacle, and how public-private partnerships can greatly expand their use.

Moving a rare disease therapy from the lab to the marketplace requires patients willing to participate in clinical trials that can demonstrate its safety and efficacy. But given the small number of people who may have a specific rare disease, finding these patients can slow the development of new therapies and create a barrier to getting treatments to patients who need them. We spoke to Sandra Shpilberg, CEO of Seeker Health, about the challenges drug companies face finding patients for rare disease drug trials, her firm’s efforts to combat that with its RarePatient database, and how the use of social media is changing the way drug developers connect with rare disease patients.

Patients with a rare disease may face debilitating, degenerative, and even life-threatening conditions, often with little treatment options. Their willingness to accept risks in the use of a therapeutic that may provide them benefit may lead to a different calculus than what regulators might consider. A study published at the end of May in the Orphanet Journal of Rare Diseases sheds light on how rare disease patients might weigh the potential benefits and risks of a therapy. We spoke to Thomas Morel, lead author of the study and a research fellow at Leuven University in Belgium, about his findings, what factors change a patient’s willingness to assume risks, and how this work might advance the discussion about the need to better consider patients’ perspectives in the regulatory process.

Gene therapy is offering rare disease patients the promise of delivering potential cures, but as it is generally approached today it has technical challenges to overcome, manufacturing complexities, and an expected high cost. Homology Medicines is taking a unique approach to gene therapy that makes use of a special set of viral vectors that gets around many of the obstacles other gene therapies face. We spoke to Arthur Tzianabos, CEO of Homology Medicines, about the company’s gene therapy, how it’s unique, and why its production and cost may be similar to other biologics today.

Orchard Therapeutics, a London-based gene therapy company with facilities in the United States, unveiled itself in May with $30 million in funding. The company is developing gene therapies to treat rare diseases involving metabolic disorders and immune deficiencies. Orchard uses a patient's own Hematopoietic stem cells, which are modified with a functioning copy of the missing or faulty gene, before being transplanted back into the patient's body. We spoke to Andrea Spezzi, chief medical officer for Orchard about the company, its approach to gene therapy, and how its addressing the challenges of bringing such treatments to market.

Mitochondria, the powerhouses of the cell, play a critical role in a range of rare and common diseases. Retrotope, a development-stage company, thinks it’s found a way to repair the damage done by various disease processes to mitochondira. The company is just concluding an early-stage trial of its experimental therapy to treat the rare disease Freidreich’s ataxia. We spoke to Bob Molinari, CEO of Retrotope, and Harry Saal, chairman of the company, about mitochondrial diseases, the approach the company is taking, and why its work may have broad implications for a wide range of degenerative diseases.

Howard Jacob understands the value of whole genome sequencing as a diagnostic tool. Jacob and his team were the first to use the technology to diagnose a child with an ultra-rare disease, which allowed doctors to save the boy’s life. Jacob, now chief medical genomics officer of HudsonAlpha Institute for Biotechnology, is working to use whole genome sequencing to find answers for other undiagnosed patients and expand the technology’s use as a clinical tool. We spoke to Jacob about the use of whole genome sequencing in the clinic, how it’s changing the way patients with rare diseases are treated, and the value of a diagnosis even in the absence of an available treatment.

Clinical trials for rare disease therapies can pose some unusual logistical challenges that can make it difficult to get patients to participate or remain enrolled in the trial until its completion. Clincierge provides a service that aim to reduce barriers to trial participation. It arranges travel and housing logistics, provides payment and reimbursement systems to address out-of-pocket expenses for patients, and supports family and caregivers to address a patient’s special needs. We spoke to Scott Gray, CEO of Clinicierge, about the challenges drug developers face in rare disease trials, what Clinicierge does to address them, and how its service reflects the growing trend toward patient-centricity.

Obsessive compulsive disorder, tics, anxiety, attention deficit hyperactivity disorder, and behaviors associated with autism spectrum disorders can be caused by a treatable autoimmune condition that is triggered by common infections. These conditions, known as PANDAS and PANS can often be misdiagnosed and wrongly treated to the detriment of the children with the condition. We spoke to Craig Shimasaki, CEO of Moleculera Labs, which has developed a diagnostic to determine if an individual’s neurologic or psychiatric symptoms could be caused by an autoimmune dysfunction. Shimasaki discussed these conditions, what we know about them, and how the availability of a diagnostic is helping change the way these patients are understood and treated.

Researchers seeking information about genes and genetic variants face the challenge of needing to search multiple databases, each with their own unique set of formatting issues. To unlock the information they are seeking, they often must spend hours wading through databases, restructuring data, and addressing nonstandard annotations. A groups of scientists at The Scripps Research Institute is addressing that problem through the development of two web services—MyGene.info and MyVariant.info—that pull data from multiple databases and provide a uniform structure for the information. We spoke to Chunlei Wu, associate professor of molecular medicine at Scripps Research Institute, about the services, the challenges in maintaining and keeping current these rapidly growing data sets, and how they are changing research into genetic-based disorders. The team's study in Genome Biology about the services can be found at http://bit.ly/1U88uAW.

Researchers’ understanding of certain rare diseases is changing as new sequencing technology is providing new views of the genome. A group of diseases collectively known as repeat expansion disorders including Fragile X Syndrome, Freidrich’s Ataxia, and Huntington’s disease are being viewed in new ways thanks to the ability to read long fragments of DNA. We spoke Jonas Korlach, chief scientific officer of Pacific Biosciences, about the company’s sequencing technology, how its changing the understanding of diseases thought to be well understood, and how it may lead to improved diagnostics and therapeutics.

While much of the attention of the Duchenne Muscular Dystrophy community has been focused on the recent FDA advisory committee review of Sarepta Therapeutics’ experimental drug Eteplirsen, Marathon Pharmaceuticals has been working to advance its own DMD drug candidate to the FDA. The company expects this month to file an application with the agency for approval to market Deflazacort, a corticoid steroid. We spoke to Tim Cunniff, head of research and development for Marathon Pharmaceuticals, about why the company thinks Deflazacort represents an improvement over existing therapies, what the company has learned from Sarepta’s experience, and its new effort to develop a precision medicine program in Duchenne.

When researchers explore the human genome, they usually look for genetic causes of disease, but a global study being led by scientists at the Icahn School of Medicine at Mount Sinai and Sage Bionetworks is looking for genes that might keep people healthy. Their study, the largest genome study to date, seeks to find people with genetic mutations that should have caused rare childhood diseases, but didn’t. Dubbed the Resilience Project, they are looking for clues in these genomes for why these people never became stricken. We spoke to Jason Bobe, associate professor and director of the Sharing Lab at the Icahn Institute and Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, about the study, what’s been learned so far, and how this may lead to new treatments for rare and deadly diseases.

For rare disease patients and their families, genome and exome sequencing may identify mutations that may be drivers of a condition, but nothing more. As families search for a name to put to a disease and look for treatments, finding others with the same condition and researchers working to understand and treat it becomes a critical part of the search for answers. Now researchers at the University of Washington have created MyGene2, a web portal for people with rare genetic mutations to connect with others with the same condition and researchers interested in their particular mutation. We spoke to Michael Bamshad, professor and chief of the Division of Genetic Medicine in the Department of Pediatrics at the University of Washington & Seattle Children’s Hospital and Jessica Chong one of the leads on the MyGene2 project at the Center for Mendelian Genomics at the University of Washington, about the portal, how it works, and what they are hoping to accomplish.

For many families with a child with a rare disease, realizing that something is wrong can be the beginning of an often long diagnostic odyssey. Typically it can take years to get a diagnosis and during that time people can find themselves isolated and without resources or support as they seek to put a name to what is wrong with their child. We spoke Amy Clugston, president of SWAN USA, about life without a diagnosis, the work of SWAN USA, and the upcoming Undiagnosed Children’s Awareness Day on April 29.

RaNA Therapeutics is pursuing treatments for rare diseases, such as spinal muscular atrophy and Friedreich’s Ataxia, with a new therapeutic approach that targets a previously unexplored druggable space. We spoke to Ron Renaud, CEO of RaNA, about his company’s effort to selectively upgregulate genes as a way to treat and prevent disease, the challenges in developing such drugs, and why the company has decided to initially target rare diseases with the technology.

Invitae is changing medical practice by brining genetic testing into the mainstream. The company says it seeks to aggregate most of the world’s genetic tests into a single service with higher quality, faster turnaround time, and lower price than many single-gene and panel tests today. The company recently announced new additions to the genes it tests for representing a major expansion of its panels for neurology, pediatrics and rare diseases. We spoke to Bob Nussbaum, chief medical officer for Invitae, about its expanded tests, how the company is able to maintain its low price point, and the implications for rare disease patients.

Emmy award-winning filmmaker Rudy Poe, in 2012, turned his lens on Hugh and Chris Hempel to document their effort to find a treatment for their twin daughters suffering from a rare lysosomal storage disorder and reform medical research in the process. The film, “Here. Us. Now.,” introduced Poe to the world of rare diseases. Now he’s in the process of taking a deeper look at the people in the rare disease community in his new film “Always in Hope.” We spoke to Poe about his interest in the rare disease world, what he’s hoping to accomplish in the new film, and how he’s using the Internet to find stories and raise money.

Large pharmaceutical companies have grown increasingly interested in rare diseases, but acquisitions of rare disease companies by large biopharmaceutical companies may lead to a cultural mismatch that hinders the development and performance of their products. We spoke to Alain Gilbert, co-chairman of the global strategic consulting firm Bionest Parnters and co-author of a February 2016 analysis in In Vivo “Orphans Should Live Alone.” Gilbert discussed how small, rare disease-focused companies operate differently than large pharmaceutical companies, the essential role their relationship with patients play, and why big companies that acquire rare disease drug developers would be best to leave them alone.

The 21st Century Cures Act, an ambitious piece of legislation of great concern to the rare disease community, passed the House last year only to stall the Senate. Now it’s back on the radar. The legislation is moving forward again, but this time in pieces. Separately in California, proposed legislation can greatly accelerate the process that tests are added to the list of newborn screening diagnostics that are performed. We spoke to Max Bronstein, senior director of public and government relations for the Everylife Foundation for Rare Diseases, about the developments on the legislative front, what the outlook is, and why these issues matter to the rare disease community.

As pharmaceutical companies, spurred by the Orphan Drug Act, have delved deeper into the development of drugs to treat rare diseases, they have forged closer ties with patient advocates. While these relationships are driven by mutual interest, tensions sometimes arise because of divergent needs. We spoke to Heather Gartman, regional managing director of InVentiv Health, about the firms recent white paper “The New Partnership Paradigm.” Gartman discussed how patient advocates can more effectively influence pharmaceutical companies, some of the mistake pharmaceutical companies make, and how the growing sophistication of patient advocates is changing the balance of power in these relationships.

In “Orphan: The Quest to Save Children with Rare Genetic Disorders,” Philip Reilly, a clinical geneticist turned venture capitalist, recounts the history of developing therapies to treat rare diseases. We spoke to Reilly, a venture partner with Third Rock Ventures, about his own experiences in the clinic treating patients with rare diseases, how his perspective has changed as a venture investor, and what the future holds in the battle against rare diseases.

Advances in sequencing the genome are unlocking mysteries about the underlying causes of both common and rare diseases. In an effort to build on existing research, The National Institutes of Health last month said it will fund a set of genome sequencing and analysis centers whose research will focus on understanding the genomic bases of common and rare human diseases. As part of this effort the Centers of Mendelian Genomics is expected to get $40 million in new funding, as well as additional monies from other NIH divisions. We spoke to Lu Wang, director of the National Institutes of Health’s Center for Mendelian Genomics, about the center’s efforts to understand rare diseases, what’s been accomplished to date, and the significance of this new round of funding.

Kelly Ranallo, a rare patient advocate in Kansas City, is using World Rare Disease Day as a way to bring together the rare disease community in the region at a town hall meeting and to use that meeting to drive new initiatives. We spoke to Ranallo about her new organization Rare KC, the upcoming town hall meeting, and her vision for turning Kansas City into the home of a national center of excellence for rare diseases.

Only 60 percent of treatments for rare disorders make it into Canada and most get approved up to six years later than in the United States and Europe, according to the Canadian Organization for Rare Disorders. In an effort to change the rare disease landscape in Canada, CORD has released a multi-pronged rare disease strategy for the country. We spoke to Durhane Wong-Rieger, president and CEO of the Canadian Organization for Rare Disorders, about the need for a national strategy, the effort to pass a regulatory framework for orphan drugs, and what it will take to make a national strategy a reality.

Rare disease patient advocates from around the world will be working to raise awareness about rare diseases on February 29, World Rare Disease Day. Last year a group of patient advocates in Utah joined forces to create a statewide effort with great success. We spoke to Gina Szajnuk, co-founder and executive director of Rare and Undiagnosed Network and Committee Chair for Utah Rare 2016, about the experience in Utah, why it was successful, and what was learned last year that’s shaping this year’s approach.

The high cost and long time it takes to develop drugs has people looking for alternative strategies for finding new treatments. One such approach is repurposing—finding new uses for already approved drugs. This is particularly compelling for rare diseases where small patient populations can serve as a disincentive to drug developers and the need for therapeutics is largely unmet. We spoke to Bruce Bloom, president and chief science officer of Cures within Reach, which launched the crowdsourcing platform CureAccelerator to fund repurposing research for rare diseases. Bloom discussed the benefits of repurposing, how the CureAccelerator will work, and why he believes the initiative could help to build a new approach to repurposing research and developing treatments for rare disease.

One of the most promising areas for rare disease treatments is gene therapy, part of the emerging area of regenerative medicine. Though long considered a therapy of the future, a number of therapeutics with the potential to treat rare diseases are advancing through the clinic. We spoke to Karen Kozarsky, managing partner at Vector Partners, ahead of the the Alliance for Regenerative Medicine’s January 27 roundtable on rare diseases. Kozarsky discussed the promise gene therapy holds for rare diseases, the challenges in developing these therapies, and the progress being made.

Rare disease research may focus on individual diseases that affect small patient populations, but often the information gleaned from this work can provide insights into far more common diseases. We spoke to Paul Schindler, executive director and CEO of the Rare Genomics Institute, about the broader benefits of rare disease research, why it can elucidate our understanding of common diseases, and the case for why this work should matter to everyone.

The Orphan Drug Act has provided critical incentives that have helped fuel the development of scores of drugs to treat rare diseases. But health experts at Johns Hopkins Medicine are calling for reform of the act to stop potential abuses by drugmakers they say have gotten huge subsidies and tax breaks for drugs that have been used far more broadly than the law intended to reward. We spoke to Martin Makary, professor of surgery at Johns Hopkins and a coauthor of a recent commentary in the American Journal of Clinical Oncology, about the Oprhan Drug Act, the unintended role it is playing in the growing controversy over drug prices, and why he thinks reform that protects the original intention of the act is needed.

The dating world can be difficult to navigate for most people, but for a woman with a variety of rare diseases, the dating world poses additional challenges. Chelsea Freund, author of The Sick and the Dating blog (thesickandthedating.com), chronicles her experiences looking for love while contending with both diagnosed and undiagnosed conditions. We spoke to Freund about her blog, the experiences she’s shared, and the advice she has for others in similar circumstances.

The gene editing technology known as CRISPR has won recognition as a powerful research tool, but a new study from scientists at The Hospital for Sick Children in Toronto is hailing the technology for its potential therapeutic applications. The study, published in the December 10 online edition of the American Journal of Human Genetics, shows how researchers, for the first time, used CRISPR to remove a duplicated gene from a genome and restored the function in the gene that causes Duchenne muscular dystrophy. We spoke to principal investigator of the study Ronald Cohn, Chief of Clinical and Metabolic Genetics and Co-director of the Centre for Genetic Medicine at SickKids, about the study, the next steps to advance the work, and the potential of the gene editing technology to be used in the treatment of a broad range of genetic diseases.

When Sam Kimura was diagnosed with the rare blood disorder aplastic anemia, she began seeking a bone marrow donor to treat her disease. Her sister Alex was more likely than someone not related to her to be a match, but testing showed she wasn’t. Not willing to passively wait for a match, the two embarked on a cross country trip to raise awareness for bone marrow transplants and encourage people to register for a database of potential donors. We spoke to Alex Kimura, executive director of Sharing America’s Marrow, about her cross country journey with her sister, the response they’ve gotten, and how they are changing people’s perception of what it takes to make a potentially life-saving bone marrow donation.

After Mike Porath and his wife received a diagnosis of a rare disease for their daughter, he said they felt lost. What helped them most, though, was talking to other parents facing the same thing they were. A career journalist, the experience eventually led Porath to create The Mighty, an online publication to help people facing disability, disease, mental illness, and chronic health conditions with the belief that real stories from real people can be empowering. We spoke to Porath about his own experience as a parent of a child with a rare disease, the evolution of The Mighty, and what he’s discovered about the benefits people get from sharing their own stories.

Sharon King, a rare disease advocate in North Carolina, saw an opportunity to accelerate the development of new therapies for patients while forging a leadership role for the state in the area of rare diseases. King, president of Taylor’s Tale, helped craft legislation that created an advisory council on rare diseases to provide guidance on research, diagnosis, treatment and education. We spoke to King and Tara Britt, associate director of the newly created North Carolina Rare Disease Advisory Council, about the development of the legislation, how it seeks to leverage the strong academic and biotechnology assets already in the state, and whether it represents a model that can be replicated elsewhere.

People often focus on the large amounts of money it takes to conduct biomedical research or develop potential therapeutics, but sometime small grants can have big impacts on the lives of people with rare diseases. Caroline Harding, CEO of Genetics Disorders UK, discusses her own journey through the rare diseases world following the birth of her son Columbus, and how she saw, through her own work, the important role small grant making could play. We spoke to Harding about her experiences, her organization’s Jeans for Genes program, and how small grants can sometimes be the catalyst to transform the lives of people.

Teenagers and young adults with chronic and rare diseases are often acutely aware of how their conditions make them different. That point can be made painfully clear by classmates and others who may avoid or bully them. Filmmaker Lisa Hedley and behavioral therapist Michelle Kupfer, both mothers raising children of difference, created Difference Diaries after a chance meeting. Through short films made by young adults with chronic and rare conditions, they are working to, as their tagline says, inspire, teach, and engage. We spoke to Kupfer about Difference Diaries, its origins, and the impact it is having.

There are about 1,000 metabolic disorders, but these genetic rare diseases can go undiagnosed in part because most doctors have so little training in recognizing them. To address this problem, the Genetic Metabolic Center for Education provides both consulting and training in the hopes of improving the diagnosis and care of these patients. We spoke to Mark Korson, medical director of the Genetic Metabolic Center for Education, about the challenges metabolic disorders pose, why so many people go undiagnosed, and how the center is seeking to fundamentally change the way that knowledge is disseminated in the hopes of increasing patient access to a diagnosis and treatment.

At the age of 21, Matthew Zachary, a college senior, concert pianist, and composer was diagnosed with a brain tumor and not expected to live long. He survived his cancer and through the experience became aware of the gap in resources for young adult cancer patients and cancer survivors. To address that gap he launched what became Stupid Cancer, an organization that focuses on the needs of this often overlooked segment. We spoke to Zachary about his own experience with cancer, the evolution of his organization, and why he considers his illness the best thing that ever happened to him.

When Karen Aiach’s daughter was diagnosed with Sanfilippo Syndrome A, a rare neurodegenerative disease, she and her husband established a nonprofit to fund research. Eventually, as the work progressed, they launched Lysogene, a biotechnology company focused on gene therapy. We spoke to Aiach, CEO of Lysogene, about Sanfilippo Syndrome A, why the focus on gene therapy, and the progress the company has made to date.

When David Fajgenbaum was in medical school he developed a rare autoimmune disease that nearly killed him. As he learned more about the state of research into the disease, he discovered researchers were all working in silos and driven by misaligned incentives. He soon abandoned his plans to become a clinical oncologist and co-founded the Castleman Disease Collaborative Network with the intent of turning the research model on its head. We spoke to Fajgenbaum, executive director of the Castleman Disease Collaborative Network and research assistant professor of medicine at the University of Pennsylvania, about his organization’s approach to research, the progress it has made in the short time it’s been around, and how it can serve as a model to other groups looking to accelerate research about rare diseases.

Genomics England, as part of its 100,000 Genomes Project, is turning to crowdsourcing to help develop gene panels to diagnose some 130 rare diseases. PanelApp, as the tool has been dubbed, creates evidence-based gene panels for rare diseases that can be downloaded and viewed by anyone. By calling on rare disease experts from around the world to review the panels, Genomics England hopes to validate and standardize the genes used to diagnose specific rare diseases. We spoke to Ellen McDonagh, lead scientific curator at Genomics England about PanelApp, why the organization has decided to use this crowdsourcing approach, and what it ultimately hopes to accomplish.

Teenage girls, under normal circumstances, wrestle with issues of identity and body image. But for young women with a chronic, rare disease, those struggles can be more complicated. That makes the wisdom, self-awareness, and self-confidence that shine through The Sick Chick blog all the more remarkable. We spoke to Shira Strongin, founder of The Sick Chick and a Global Genes 2015 honoree for teen advocacy, about her battle with Ehler-Danlos Syndrom, how she’s come to appreciate what her disease has taught her, and her work with other teen rare disease advocates to form We Are More, an effort to convey to the media and public that teens with chronic illnesses are defined by more than their diseases.

The rare disease community in July celebrated the passage in the House of the 21st Century Cures Act, legislation that promises among other things to accelerate the development of drugs to treat rare diseases. But the legislation appears to be stalled in the Senate as the clock is running and concern growing that it may not be getting the attention it needs to push it across the finish line. We spoke to Max Bronstein, senior director of public and government relations for the Everylife Foundation for Rare Diseases, about the legislation, where it stands today, and what it will take to see it become law.

For 20 years, Lisa Bentley competed as a professional triathlete with impressive results. She won 11 Ironman races, 11 half Ironman races, had several top five finishes at the Ironman World Championships, and represented Canada on multiple National Teams and at the Pan American Games. For a decade, Bentley ranked number five in the world. All of that is all the more impressive considering Bentley did so with cystic fibrosis, a rare genetic lung disease results in chronic infections and limits lung capacity. We spoke to Bentley about life as a competitive athlete with cystic fibrosis, how she managed her disease with her physically demanding pursuits, and her life now as a patient advocate.

Caregivers, an often overlooked part of the healthcare continuum, play a critical role in the world or rare diseases. But with this role, usually taken on by family members, comes physical, emotional, and financial stress. We spoke to Grace Whiting, Director of Strategic Partnerships for the National Alliance for Caregiving, her organization’s study of caregivers, the issues they face, and policy changes needed to better support them.

The emergence of gene therapy is giving hope of new treatments for rare diseases. Abeona Therapeutics is one of a new generation of therapeutics companies working to address life-threatening rare diseases with this new therapeutic approach. We spoke to Michelle Berg, vice president of patient advocacy for Abeona, about the company, its pipeline, and the hope gene therapy holds for addressing rare diseases.

Travis Flores has had a lifelong battle with cystic fibrosis, a genetic disease that causes a buildup of mucus in the lungs and other organs and can lead to respiratory failure and problems in breaking down food and absorbing nutrients. Flores, who recently underwent a double lung transplant, continues to pursue his interests as an artist, philanthropist, and patient advocate. We spoke to Flores about his experiences, how rather than being a barrier, his disease has served as a source of motivation, and how he’s learned to live with, rather than for, his disease.

When Matt Wilsey daughter Grace was diagnosed with the ultra rare disease NGLY1 deficiency, he travelled the world to get a diverse group of researchers to work on finding answers. His approach to driving research, he says, comes from his experience as a Silicon Valley entrepreneur. We spoke to Wilsey about the experience getting a diagnosis for his daughter, what he learned from others who had gone before him, and the importance of open collaboration across institutions.

Genome, a quarterly magazine launched in 2014, is an effort to bring an understanding of the revolution driven by new insights into human genetics to patients, their families, and caregivers. It seeks to tackle complex issues in an accessible way to empower medical consumers and help them make better decisions about their own care. We spoke to Jeanette McCarthy, editor-in-chief of Genome, about the magazine, it history and goals, and how the scientific advances it tracks are forever changing the nature of medicine.

Scot Langley, better known as Froggy to listeners of the syndicate radio show Elvis Duran and the Morning Show, learned in 2010 he had acromegaly, a rare, debilitating endocrine disorder caused by a non-cancerous pituitary tumor that triggers overproduction of two hormones that stimulate growth. Langley had been living with unexplained symptoms for 10 years, including profuse sweating and debilitating headaches. He also watched his feet, hands and jaw grow abnormally without understanding why. We spoke to Langley about his path to a diagnosis, his life since then, and why has decided to be so public about his condition.

The Internet giant Google has set its sights on revolutionizing how researchers store, analyze, and share genomic data. The company recently entered into an agreement with the Broad Institute that allows it to integrate Broad’s Genomic Analysis Toolkit into Google Genomics. We spoke to David Glazer, director of engineering for Google, about its Google Genomics platform, the opportunity it sees in genomics, and what it’s doing to help researchers turn vast amounts of data into actionable information.

The FDA Office of Orphan Products Development seeks to advance the evaluation of drugs and diagnostics to treat rare diseases. A growing toolkit of incentives has helped drive the development of new products for rare diseases, but the need remains great. We spoke to Gayatri Rao, director of the FDA’s Office of Orphan Products Development, about the rare disease landscape, how scientific developments are reshaping clinical trials and the use of biomarkers, and what the agency is doing to better incorporate patients’ perspectives into the drug review process.

The world of healthcare is changing and patients today are taking a greater role in determining and coordinating their own care. Technology is playing a critical role in enabling the new patient of today and Yabidu and its online care notebook is an example of the types of tools allowing patients to become active participants in the process. We spoke to Todd Kozikowski, CEO and founder of Yabidu, about the company, how patients use its platform, and the ways technology is allowing patients to take control of their own healthcare

Bonner Paddock led an active childhood despite his physical limitations. After years of being misdiagnosed, he learned at age 11 that he had cerebral palsy, a nonprogressive brain injury that affects muscle movement and coordination. Rather than accept his physical limitations, Paddock went on to become the first person with cerebral palsy to climb Mt. Kilimanjaro, the tallest freestanding mountain in the world. He also went on to become an elite triathlete when he competed in the Kona Ironman. We spoke to Paddock about his story, his efforts to raise awareness and support for children with disabilities through his OM Foundation, and how he is working to empower children with disabilities and their families to live life beyond limits.

On February 28, World Rare Disease Day, Noah Coughlan set out on a 3,100 mile run across America from New York City to San Diego’s Ocean Beach. The goal was to raise awareness for rare diseases. On July 4, right on schedule, he finished his run entering the water in San Diego before a crowd of supporters. We spoke to Coughlan, founder of the Run4Rare Foundation, about his efforts to raise awareness for rare diseases, his recent run, and how he plans to continue his efforts.

Patients, long passive participants in the drug research and development process, are playing a more active role, and the value of their input is being recognized by researchers, drugmakers, and regulators. The 21st Century Cures Act, sweeping legislation now pending in Congress, would help solidify that role by providing opportunities for patient input into the regulatory process. We spoke to Kim McCleary, managing director of FasterCures, about the legislation, why it matters, and how it will change the role of patients.

Fibrocell Science is developing cell and gene therapy to treat rare skin and connective tissue diseases. The company recently reported encouraging pre-clinical results on its gene therapy for RDEB a congenital, progressive, and debilitating genetic disorder that leads to death. The data sets the stage for Fibrocell and its partner Intrexon to advance the experimental therapy to human clinical trials. We spoke to David Pernock, chairman and CEO of Fibrocell about the company, its cell and gene therapies, and how these technologies promise to bring new approaches to treating devastating diseases.

Patent filings in the area of rare diseases suggest government incentives have worked to spur innovation, according to a new report from the international intellectual property firm Marks & Clerk. The report examines patent filings in the areas of rare diseases, antibiotics, and vaccines. We spoke to Gareth Williams, partner and European patent attorney with Marks & Clerk, about the report, the role Big Pharma is playing, and some surprises on the list of top filers of rare disease related patents.

Disruptive changes to the healthcare landscape are creating new tensions in the traditional relationship between pharmaceutical companies and patient advocacy groups, according to the findings of a report from InVentiv Health. The report, based on interviews with nearly four dozen representatives of patient advocacy organizations, finds patient advocates expect greater transparency from their pharmaceutical partners, want to play an increased role in clinical trial design and execution, and see a role for themselves in education campaigns for patients and providers. We spoke to Heather Gartman, regional managing director of InVentiv Health, about the report, the changing dynamics between pharmaceutical companies and patient advocacy organizations, and whether the long-term health of the symbiotic relationship is in jeopardy.

Bellus Health was originally formed around technology seen as the basis for promising therapeutics for Alzheimer’s disease, but the company also pursued rare disease opportunities as well. Despite encouraging results, the financial crisis made it difficult for the company to advance its potential Alzheimer’s therapy. With a new CEO put in place, the company overhauled its strategy, out licensed its alzheimer’s drug and embraced its identity as a rare disease drug company. We spoke to Roberto Bellini, CEO of Bellus Health, about the transformation of the company, the changing environment for orphan drugs, and why being a rare disease drug company is an attractive business model today.

The Lion’s Mouth Opens, Lucy Walker’s critically acclaimed short documentary, begins at a dinner between the actress and filmmaker Marianna Palka and her friends the night before she gets results from a genetic test that will tell her whether she carries the gene for Huntington’s disease. Palka’s father has had a long battle with the neurodegenerative disorder and she has a 50 percent chance of having the gene that causes it. As the film readies to debut on HBO June 1 at 8 p.m., we spoke to Palka about her decision to document her experience, why she chose to be tested, and whether it is better to know or not know. Because of the nature of the film, we have agreed not to discuss her test results in consideration of listeners who may not yet have seen the film.

Royal Pains, the television program about a concierge doctor in the Hamptons, begins its seventh season on the USA Network June 2. As the new season begins, the shows is expected to take an increased focus on rare diseases as the mysterious billionaire Boris Kuester von Jurgens-Ratenicz has decided to fund a rare disease research center. We spoke to Royal Pains Executive Producer Michael Rauch, Executive Producer Carol Flint, and series star Mark Feuerstein, about the show, the role rare diseases have played on it, and how rare disease themes may play out in the episodes ahead.

Nick Sireau’s efforts to find a cure for his children’s rare genetic disease alkaptonuria caused him to confront struggles faced by many people within the rare disease community as they seek to raise funds, foster research, and learn about running clinical trials and supporting patients. The experience led him to create Findacure, an organization that seeks to train, mentor, and empower patient groups. We spoke to Sireau, chairman of Findacure, about the organization, where it is focusing its efforts, and why he prefers the term “fundamental” diseases to “rare diseases.”

MPS I is a rare genetic disease that is incurable and lethal by age 12. Seattle-base Immusoft thinks it can harness a key part of the immune system to manufacture a missing enzyme needed to treat the disease. It represents a broader effort on the part of the company to develop a platform to treat a wide range of disease by turning immune system cells into drug factories. We spoke to Matthew Scholz, CEO of Immusoft, about the company’s work, the process for programming these cells, and how the inspiration for its approach came from the computer industry.

The legendary Notre Dame football coach Ara Parseghian lost three of his grandchildren to Niemann-Pick Type C, a rare and fatal genetic disease. Parseghian’s story has helped mobilize members of the Notre Dame community, and in particular, Greg Crawford, Dean of the College of Science and professor of physics, in a fight against the disease. Crawford has been named a finalist in the Biotechnology Industry Organization’s Everyday Superheros contest in recognition for his work in raising funding and awareness to combat Niemann-Pick Type C. We spoke to Crawford about his involvement with the disease, his series of cross country bike rides for the cause, and what advice he’d offer other patient advocates looking to raise money and awareness.

Last month Utah Governor Gary Herbert signed into law the Right to Try Act, which provides terminally ill patients access to experimental drugs that have completed at least early-stage clinical testing. Utah is the tenth state to pass such law and a growing list of other states are considering similar legislation. We spoke to Jonathan Johnson, founder of Utah’s Right to Try Foundation, about the law, how it works, and the difference he expects it will make for patients who have exhausted available therapeutic options.

When a doctor delivered a devastating diagnosis to Pat Furlong for her two sons with Duchenne Muscular Dystrophy, she refused to sit by and just watch them slowly die. She marched off to Washington to corner her Senator and the director of the National Institutes of Health, borrowed money to fund her sudden role as a patient advocate, and brought together academic researchers to get them thinking on how they could tackle the disease. We spoke to Furlong, founding president and CEO of Parent Project Muscular Dystrophy, about her experiences, what patient advocates can do to raise awareness for their causes, and how they should think about best leveraging their investments.

Lysosomal storage disorders are a group of genetic rare diseases that can manifest themselves in a diverse set of symptoms and can be difficult to diagnose. Now Courtagen Life Sciences has brought to market LysoSEEK, a next-generation genetic tests for sequencing 94 genes associated with nearly 60 metabolic disorders. The new test provides an alternative to the piecemeal testing that can provide a long, slow, and costly path to an answer. We spoke to Richard Boles, medical director of Courtagen, about this group of diseases, the importance a faster diagnosis can play in minimizing irreversible damage, and how the new test changes the diagnostic landscape for these patients.

David Pearce created the Coordination of Rare Diseases at Sanford or CoRDS registry as a national resource that could help accelerate research into rare diseases. We spoke to Pearce, president of Sanford Research, director of Sanford Children’s Health Research Center, and the Global Genes 2012 Champions of Hope honoree for Research & Science, about his own research into the neurodegenerative disorder Batten Disease, how that led to the development of CoRDS, and the role patient registries can play in accelerating rare disease research and the development of new therapies.

Carri Levy’s search to find answers to her daughter’s lifelong illness was made worse by doctors that insisted there was no problem. A producer for the daily morning show The Balancing Act on Lifetime TV, Levy launched the series Behind the Mystery: Rare and Genetic, in effort to search for answers to her daughter’s illness. As part of a series of podcasts revisiting past winners of Global Genes’ Champions of Hope award, we spoke to Levy, a 2013 advocacy honoree, about her search for a diagnosis for her daughter, her own transformation into being a patient advocate, and what effect connecting to the rare disease community through her television show has had on her.

As a child, Sami Petersen developed progressive scoliosis, a severe curvature of the spine as a result of a rare genetic disease. The condition eventually led to complex spinal surgery to correct the worsening deformity, pain, and complications. As she recovered from her operation, Petersen, who was 15 at the time, decided to launch the organization SHIFT Scoliosis, which has grown from a small awareness initiative to an organization that is reaching thousands of people through its education, awareness, and outreach programs. As part of a series of podcast revisiting past winners of Global Genes Champions of Hope award, we spoke to Petersen, a 2014 teen advocacy honoree, about her experience with scoliosis, what led her to launch SHIFT, and how she’s reaching people around the world.

The U.S. Food and Drug Administration approved more than 230 new drugs to treat rare diseases in the past decade and there are currently more than 450 orphan drugs in development, according to a new report (http://onphr.ma/1EsGJw6) from the Pharmaceutical Research and Manufacturers of America. Though developing drugs for rare diseases presents many challenges, policy changes and scientific breakthroughs have helped changed the landscape. We spoke to Gretta Stone, Deputy Vice President of Policy and Research at PhRMA, about the report, how the Orphan Drug Act encouraged investment in R&D for rare diseases, and what fuels her optimism for drug development efforts to combat this group of diseases in the years ahead. Also, we check in with Run4Rare's Noah Coughlan as he continues his 3,100 mile run across the country to raise awareness for rare diseases.

Though there are almost 7,000 rare diseases, less than 500 drugs have been approved to treat any one of them. What that means for millions of people with a rare disease is that there’s no approved treatment they can use. There is, however, a growing effort to look at drugs approved for other uses and repurpose them to treat rare diseases in which they might be effective. We spoke to Julia Jenkins, executive director of the EveryLife Foundation for Rare Diseases about why repurposing approved drugs could greatly increase the available treatments for rare diseases, what draft legislation would do to encourage drugmakers to pursue these opportunities, and why experiences from past legislation suggest the approach could be quite effective.

Recursion Pharmaceuticals has set the audacious goal for itself of developing 100 drugs in 10 years for rare diseases. The company, focused on repurposing compounds abandoned in clinical development by other drugmakers, thinks it can achieve this by a fundamentally different approach to drug development than the industry’s traditional process of screening compounds against potential disease targets. We spoke to Chris Gibson, founder and CEO of Recursion, about the approach his company is taking, whether rare diseases particularly lend themselves to it, and whether it has implications more broadly for drug development.

Noah Coughlan will set out on a 3,100 mile run across America from the Statue of Liberty to San Diego’s Ocean Beach in the hope of raising awareness and support in the fight against rare diseases. It will be the third run across the country for the founder of the Run4Rare Foundation and begin on February 28, World Rare Disease Day. We spoke to Coughlan about his run, what motivated him to do this, and what he hopes to accomplish.

The search for cures for diseases is limited by the ability of scientists to consume and understand the rapidly expanding volumes of biomedical literature produced each year. Andrew Su, associate professor in the department of Molecular and Experimental Medicine at The Scripps Research Institute, has a solution. He wants to enlist members of the rare disease community and general public to become citizen scientists and pour through biomedical journals to help find connections and identify research in one area that may shed light on another. We spoke to Su about his project Mark2Cure, the role crowdsourcing can play in accelerating rare disease research, and why members of the rare disease community may better suited for elucidating important findings than supercomputers.

World Rare Disease Day, an annual observance held on the last day of February, seeks to raise awareness for rare diseases. On that day, hundreds of patient organizations from more than 80 countries will be participating in activities to call attention to thousands of ailments, many of which are without treatments or even names. We spoke to Hudson Freeze, director of the Human Genetics Program at Sanford Burham Medical Research Institute, about World Rare Disease Day, the importance of raising awareness, and how research into rare diseases can shed light into more common ailments.

At the age of 8, Bill Elder, Jr. was diagnosed with cystic fibrosis, a rare, genetic disease expected to cut his life short. Now a third year medical student, Elder has been the beneficiary of Vertex Pharmaceutical’s Kalydeco, an example of the transformative effects personalized therapies can have on patients. As President Barack Obama announced plans for a precision medicine initiative during his State of the Union address, Elder sat alongside First Lady Michelle Obama as a living and breathing testament to the promise of precision medicine. We spoke to Elder about his recent visit to Washington, his experience with cystic fibrosis, and the difference Kalydeco has made in his life.

The combination of high cost, long development times, and small patient populations for rare diseases is driving new models to accelerate drug development. The story of the newly formed rare disease company Vtesse is a compelling example. Driven by parents, advanced to the clinic by the National Institutes of Health, and licensed by a new company formed out of an orphan drug accelerator, Vtesse is advancing an experimental drug to treat Niemann Pick Disease Type C and other lysosomal storage disorders. We spoke to Ben Machielse, CEO of Vtesse, about his company, the unusual collaborations that led to its formation, and what it says about how patients, government, investors, and industry can work together to speed the development of new therapies for rare diseases.

Crowdfunding, once thought of as little more than a way to raise money for small scientific projects, is increasingly being used to raise significant capital to fund startups. Perlstein Lab, a San Francisco-based starup focused on finding new drugs to treat rare diseases, raised more than $2 million using crowdfunding. We spoke to Ethan Perlstein, founder and CEO of Perlstein Lab, about his company, the potential of crowdfunding, and the unusual role social media has played in his efforts to raise capital.

Ilan Ganot is not your typical biotech entrepreneur. When his son Eytani was diagnosed with Duchenne muscular dystrophy, he quit his job as a hedge fund manager with JPMorgan in London, relocated his family to Boston, and launched a company focused exclusively on finding treatments for Duchenne. We spoke to Ganot, CEO and founder of Solid Ventures, about his company, the thinking behind his business model, and whether his approach is transferable to other rare diseases.

Prosensa, a biotechnology company developing a breakthrough therapy for the rare, fatal, genetic disease Duchenne muscular dystrophy suffered a big setback when disappointing, late-stage trial results of its lead therapeutic led its partner, GlaxoSmithKline, to return rights to the experimental drug in January 2014. Prosensa’s stock plummeted and the future of the company was uncertain. CureDuchenne, which had provided early funding for the company, stepped in once again. This time it made a $7 million commitment to restore the clinical programs and move the company forward. We spoke to Debra Miller, president and CEO of CureDuchenne about her experience with Prosensa, the recent news that BioMarin would acquire the company for up to $840 million, and the role venture philanthropists like her can play in accelerating the development of life saving drugs.

News last month of the Cystic Fibrosis Foundation’s $3.3 billion sale of royalty rights to Kalydeco and other Vertex Pharmaceuticals drugs it helped fund served as a bold statement to the growing prominence and power of venture philanthropy. We spoke to Margaret Anderson, executive director of FasterCures, about the transaction, the role new funding and collaboration models are playing in accelerating drug development, and what traditional investors and disease groups are learning from each other.