RARECast

Epicrispr Biotechnologies is using CRISPR to modulate the expression of disease-causing genes without making cuts to DNA. Its lead program is in development to treat FSHD, a genetic disorder that causes progressive weakness in the muscles of the face, shoulders, and upper arms. We spoke to Amber Salzman, CEO of Epicrispr, about how its one-and-done therapies work to target the epigenome, the company's lead program in FSHD, and the broader applications for its therapeutic approach.

One of the hallmarks of the rare genetic disorder Prader-Willi syndrome is hyperphagia, an insatiable desire to eat. Households with someone with Prader-Willi syndrome often have to take measures to restrict access to food, such as locking refrigerators, pantries, and trash cans. They must also deal with the complex behavioral challenges associated with the condition. Earlier this year, Soleno Therapeutics won approval for VykatXR, the first FDA-approved therapy for treating hyperphagia. We spoke to Anish Bhatnagar, CEO of Soleno Therapeutics, about Prader-Willi syndrome, its therapy to treat the condition, and the significance of having a medicine that can address hyperphagia associated with the disorder.

CTX is a rare metabolic disease that can cause seizures, developmental delays, and intellectual disability. Now, a diagnostic test that can detect the condition early is available, and a treatment that can prevent the disease's serious effects has won regulatory approval. We spoke to Bart Duell, professor of medicine at Oregon Health Sciences University, about CTX, the role OHSU played in developing a diagnostic and advancing a treatment for CTX; and the critical interplay between academic medical centers, patient advocates, and drug developers to address the needs of people with rare diseases.

Biliary tract cancers are a group of rare cancers with limited treatment options and generally poor outcomes because most patients are diagnosed at an advanced stage. There are efforts to address that through the development of early detection tools. And the use of biomarker testing can today match as many as half of these patients to a targeted therapy, although it's critical to make people aware of the importance of this. We spoke to Rachna Shroff, associate director of clinical investigations of the gastrointestinal clinical research team at the University of Arizona Cancer Center, about biliary tract cancers, the importance of biomarker testing, and what can be done to improve outcomes for people with these rare cancers.

Drug development activities focused on the rare, neuromuscular condition Duchenne muscular dystrophy have translated into functional improvements and an extension of life expectancy. Regenxbio is among several companies pursuing a gene therapy to treat Duchenne. Regenxbio believes both its microdystrophin—a truncated form of the dystrophin gene­ small enough to fit in a vector­—and the vector it is using, give it a competitive advantage over other efforts. We spoke Curran Simpson, CEO of Regenxbio, about the company's platform technology, the advantages he sees with its experimental DMD gene therapy, and how a partnership announced at the start of 2025 focused on a pair of other gene therapies provided a welcome alternative to tapping the capital markets.

GRIN-related disorders are a group of rare neurodevelopmental conditions that can cause intellectual disability, behavioral challenges, and seizures. GRIN Therapeutics is developing a once-failed development candidate for chronic neuropathic pain, known as radiprodil, as a potential treatment for GRIN-related disorders driven by gain-of-function mutations. We spoke to Bruce Leuchter, president and CEO of GRIN Therapeutics, about GRIN-related disorders, how the company came to develop radiprodil, and how it represents an effort by Neurvati Neurosciences to bring a portfolio approach to developing novel treatments for neurological and psychiatric disorders.

Osteosarcoma is a rare and aggressive bone cancer that usually affects children and teenagers. Over the past 40 years, there's been little progress to improve survival rates, with the five-year survival rate stagnant at about 60 to 70 percent for localized disease and 15 to 30 percent for metastatic osteosarcoma. OS Therapies is developing an experimental immunotherapy to treat certain osteosarcomas. We spoke to Paul Romness, president and CEO of OS Therapies, about why osteosarcomas have been difficult to treat, the company's experimental therapy for the condition, and the promising results that have been seen to date.

When Paul Biderman was born, he had trouble gaining weight. He grew sicker and, at about six months, he was diagnosed with the ultra-rare genetic disease abetalipoproteinemia, a condition that impairs a person's ability to absorb fats and fat-soluble vitamins. The condition requires adherence to a strict diet and a regimen of daily vitamin supplementation, which he didn't always follow. Now approaching 60, Biderman suffers from neuropathy in his lower limbs and is losing his eyesight. We spoke to Biderman, chief operating officer and patient liaison for the ABL+ Foundation, about living with ABL, the challenges of obtaining adequate nutrition, and the impact becoming a patient advocate has had on him.

Spinocerebellar ataxia includes a group of rare, genetic, neurodegenerative disorders. People with the condition suffer from the loss of balance, coordination, and muscle control. As the condition progresses, people can lose the ability to walk and speak. There is no approved treatment for SCA, but Biohaven has applied to the U.S. Food and Drug Administration to begin marketing its experimental therapy troriluzole, which can normalize levels of glutamate, a key neurotransmitter implicated in the disease. We spoke to Melissa Beiner, senior medical director at Biohaven, about spinocerebellar ataxia, the company's therapy under review at the FDA to treat the condition, and why it may have the potential to benefit a number of other neurological conditions as well.

Netherton syndrome is a rare and chronic skin condition. One in ten infants with the disease will die as a result of infections and related complications. Azitra has developed a platform for engineering bacteria that naturally colonize the skin to produce proteins with therapeutic benefits to treat Netherton syndrome and other conditions. We spoke to Travis Whitfill, co-founder and chief operating officer of Azitra, about Netherton syndrome, the company's platform technology for engineering live biotherapeutic products, and why it takes more than simply inserting a gene into a desired bacteria to produce these treatments.

Emerging cell and gene therapies represent areas of great promise for people with rare, genetic diseases, but the translation gap for these medicines can leave them stalled at the lab. Mass General Brigham in 2022 launched the Gene and Cell Therapy Institute, a research hub dedicated to advancing gene and cell therapies for various diseases to bridge the divide between academic labs and clinical development of therapies. The institute brings together more than 500 researchers and clinicians and boasts unique assets, such as its RNA Therapeutics Core, which enable it to produce cutting-edge circular RNA on-site. We spoke to Nathan Yozwiak, head of research at the Mass General Brigham Cell and Gene Therapy Institute, about the need it is seeking to address, how the institute operates, and what it might do to enable the development of bespoke therapies for ultra-rare diseases.

Raziel Green lost both her mother and aunt to the rare neurodegenerative disease amyotrophic lateral sclerosis or ALS. But when Green, a runner, began experiencing muscle weakness and falls, doctors failed to recognize that she had a genetic form of the condition. Two years after she first sought care, she was diagnosed with the SOD1 form of the disease and enrolled in a clinical trial of what would become the antisense oligonucleotide Qalsody. We spoke to Green about her experience with ALS, her decision to enroll in a clinical trial, and her health more than eight years after her diagnosis.

While traveling in Australia, Russ Walter was taken to the hospital and treated for heart palpitations. When he returned home, he soon lost the ability to walk. He was diagnosed with the rare autoimmune condition Guillian-Barre syndrome and spent three months in intensive care and rehabilitation. It would take nearly a year of physical therapy before he could walk again. We spoke to Walter, liaison and board member of the GBS-CIDP Foundation International, about his recovery from Guillian-Barre syndrome, the changing medical landscape for the condition, and why his experience led him to become a patient advocate

Organoids, three-dimensional cell models that can replicate an individual's organs, are valuable tools for testing medicines that might treat their illness. It can, however, take up to $10,000 and a year to grow organoids using conventional methods from patient-derived induced pluripotent stem cells. Researchers at Children's Mercy Kansas City's Genomic Medicine Center developed a way to do this from about $200 and in two to three weeks. We spoke to Scott Younger, director of disease gene engineering at Children Mercy Kansas City's Genomic Medicine Center, about the process, the test it ran to match three children with Duchenne muscular dystrophy to an antisense oligonucleotide therapy, and the potential impact this may have on developing customized therapies for people with rare genetic diseases.

IgA nephropathy is a rare autoimmune kidney disease that can lead to the loss of kidney function. Though a number of treatment options exist today, none address the root cause of the disease and instead seek to manage symptoms, slow progression, or prevent complications. Vera Therapeutics' experimental fusion protein atacicept, in a phase 2B study, showed the ability to provide long-term kidney function stabilization. We spoke to Marshall Fordyce, founder and CEO of Vera Therapeutics, about IgA nephropathy, atacicept, and its potential in other B cell-mediated diseases.

When Katrina Rice's son was diagnosed with the rare, hematological disorder sickle cell disease, she got to spend a lot of time understanding how a rare disease affects the daily life of people with a condition and their caregivers. Her son, now 28, has become a participant in clinical trials, and that's further broadened Rice's perspective as chief delivery officer of biometrics services at the clinical trial data management and analytics company eClinical Solutions. We spoke to Rice about sickle cell disease, how her experience as a mother of a child with a rare disease has informed her professional life, and how she has used that to educate her colleagues and clinical trial sponsors about how to better engage with rare disease clinical trial participants.

In 2023, Acadia Pharmaceuticals won approval for Daybue, the first and only treatment for the rare, neurodevelopmental disorder Rett syndrome. Daybue is not a cure and Acadia continues to pursue additional therapies for the condition including an antisense oligonucleotide therapy to upregulate a protein people with Rett syndrome lack. We spoke to Liz Thompson, executive vice president and head of research and development for Acadia, about Rett syndrome, how Daybue has changed the treatment landscape for people with the condition, and the company's advancing pipeline to treat it.

When Patty Keating had her thyroid removed, she experienced what she described as a “buzzing in her face,” had trouble sleeping, and felt anxious. Her symptoms grew worse and she had trouble climbing stairs. Then, six months later, her heart started racing, and her husband rushed her to the hospital, where tests showed she was having a heart attack. But when doctors performed catheterization to clear a blockage, they found there was none. It was then that she was diagnosed with hypoparathyroidism. Hypoparathyroidism is often underdiagnosed and undertreated rare condition. While it can have a genetic cause, it can also result from surgery or injuries to the neck that damage the parathyroid glands. These glands are a group of four, pea-sized objects at the back of the thyroid that create a hormone that plays an essential role in regulating blood calcium levels. The absence or damage of these glands can cause a wide range of health problems. We spoke to Keating, executive director of the HypoPARAthyroidism Association, about her experience with the condition, why it can be challenging to diagnose, and the changing treatment landscape.

Earlier this year iECURE reported that an infant with the rare and deadly liver disease OTC deficiency had a complete response to its experimental gene editing therapy. It is believed to be the time that an infant was treated with an in vivo, liver-directed gene editor. The treatment restored ammonia levels in the child's blood to normal and the child is off of ammonia scavenger medicines and is eating a normal diet. We spoke to Joe Truitt, CEO of iECURE, about the company's experimental therapy for OTC, how it works, and its approach to in vivo gene editors.

Healx, which developed an AI platform to repurpose drugs for rare diseases, is among the first generation of companies built on an AI drug discovery engine. The company's lead experimental therapy, which the U.S. Food and Drug Administration granted Fast Track designation to in October 2024, is in mid-stage development for neurofibromatosis type 1, a rare genetic condition that causes tumors to grow on nerves. A deal at the end of 2024 shows expanded uses for its platform technology as Sanofi entered into an agreement to see if the company could find new indications for a late-stage asset that it had discontinued. We spoke to Tim Guilliams, co-founder and CEO of Healx, about the origin of the company, its lead asset in development for neurofibromatosis type 1, and how he views the company's progress to date.

Primary immunodeficiency disorders include more than 400 conditions, and a growing number of people are being recognized as having them as a result of improved diagnostic tools and greater awareness among physicians. Most treatments for these conditions are plasma-derived therapies sourced from donors. We spoke to Joerg Schuettrumpf, chief scientific innovation officer at Grifols, about the changing landscape for these conditions, the challenges of ensuring a reliable supply of plasma-derived therapies, and how treatment options may evolve.

In November, Citizen Health unveiled itself with $14.5 million in funding and a partnership with the Chan Zuckerberg Initiative. A reinvention of what began life as Ciitizen, Citizen Health takes a sharp focus on rare disease, a departure from its precursor, which was initially envisioned as a tool for cancer patients to gather all of their health data in a single place. We spoke to Citizen Health Co-Founders Farid Vij and Nasha Fitter about the evolution of Citizen Health, what it will enable, and how it is helping shift power towards patients and their caregivers in the pursuit of new therapies.

Michelle Teng, a techbio entrepreneur, co-founded the H-ABC Foundation after her daughter was diagnosed with the ultra-rare and fatal leukodystrophy. The foundation funded research that identified the causal mutation of the condition and pointed the way to a potential therapy. Teng later joined with Dan Williams to co-found SynapticsBio to advance that work and develop an experimental antisense oligonucleotide therapy to silence the mutated gene underlying a form of the progressive neurological condition. We spoke to Williams, co-founder and CEO of SynaptixBio, about H-ABC, how the company's experimental therapy works, and the role patient advocates have played in the company's efforts to advance its experimental therapy.

Gene therapies that use viral vectors generally are not redosable because once patients are exposed to the virus used to insert the gene, their immune system will become activated against them. Immusoft is using a patient's own B cell and engineering them to produce needed proteins by transforming them into biofactories without the use of a viral vector. The company's lead experimental therapy is an autologous B cell therapy engineered to produce the enzyme that people with the rare lysosomal storage disorder MPS I are deficient. We spoke to Sean Ainsworth, CEO of Immusoft, about MPS I, the limits of existing enzyme replacement therapies, and the potential benefits of using engineered B cells to treat people with the metabolic disorder and other conditions.

BridgeBio has been an innovator in applying portfolio theory to its business model as a way to broaden access to capital. The company recently had a big win with its approval for Attruby, its treatment for the rare condition transthyretin amyloidosis cardiomyopathy. The approval is a boost for the company, which, like many biotechs, had to scale back on programs in the face of the downturn in capital markets in recent years. We spoke to Neil Kumar, co-founder and CEO of BridgeBio, about the approval of Attruby, the company's late-stage pipeline, and what he's learned about its business model in the process.

The Genomic Answers for Kids program at Children's Mercy Kansas City has increased access to cutting-edge genomic sequencing for children suspected of having rare genetic diseases and improved the diagnostic yield of these tests. The program has collected samples from 8,000 rare disease patients and their family members and diagnosed about 2,000 people to date. Nevertheless, payers have been reluctant to increase reimbursement rates for more comprehensive genomic testing, posing a challenge to its sustained and expanded use for children who can benefit from it. We spoke to Tomi Pastinen, director of the Center for Pediatric Genomic Medicine at Children's Mercy Kansas City, about the success of the program to date, the reimbursement challenges, and the future of the technology.

Anthony Moncao takes part in weightlifting and crossfit competitions, but that came only after he was diagnosed at the age of 19 with the rare, neuromuscular condition Friedreich's ataxia. As the condition progressed, he had to give up on his plans of becoming at tattoo artist. Once he became reliant on a wheelchair, he began to withdraw from the world, not wanting people to see his disability on full display. That changed when he went with a friend on an extended cross-country trip that provided him with a new outlook on life. We spoke to Monaco about coming to terms with his diagnosis, how he was forced to abandon some dreams, and how was able to find new ones to pursue.

Genethon, the non-profit gene therapy developer created by the patient association AFM-Telethon, began working with Sarepta Therapeutics in 2017 to develop a gene therapy for the rare neuromuscular condition Duchenne muscular dystrophy. Now that Sarepta has won approval for a separate gene therapy to treat the condition, Genethon is advancing development of its experimental gene therapy on its own. We spoke to Frederic Revah, CEO of Genethon, about Duchenne, the organization's efforts to complete clinical development of its gene therapy for the condition, and how it might commercialize the treatment.

In “More than We Expected: Five Years with a Remarkable Child,” James Robinson recounts the life and death of his son Nadav, who was born with a congenital heart condition. The book follows the family's efforts to address and manage Nadav's rare condition. As tragic as losing a child is, Robinson says his book is not a sad story. In fact, the book is filled with Robinson's encounters with the wonders of parenthood, human kindness, and unexpected connections. We spoke to Robinson about his experience as the father of a child with a rare disease, life in hospital wards across two continents, and the feeling of pride in his son that remains.

Noam Baumatz entered the world of gene therapy as a father in pursuit of a life-savings treatment for his daughter Noga, who was born with an ultra-rare immunodeficiency. Though she died before a treatment could be developed, Baumatz launched Noga Therapeutics to try to help others in the rare disease community. The company's platform technology uses lentiviral-based vectors to genetically reprogram blood stem cells. It is developing therapies for both rare and common diseases. We spoke to Baumatz about his experience with his daughter, the vision for Noga Therapeutics, and the company's business decision to pursue both rare and common diseases.

The work of Boston Children's Hospital's Timothy Yu to develop a customized antisense oligonucleotide to treat Mila, a child with an ultra-rare neurodegenerative disease, created much excitement for the potential of N-of-1 therapies. Julia Vitarello, Mila's mother, has talked about going from Mila to millions and co-founded EveryONE Medicines to enable the development of individualized therapies on a large scale. Earlier this year the company named industry veteran Kent Rogers as its CEO. We spoke to Rogers about the challenges of building a sustainable business model for the development of individualized therapies, the regulatory hurdles it may face, and what it will take to get payers to embrace such medicines.

For some genetic diseases, there is not only the need to replace the function of a gene that is lost, but to also address toxicities that a mutated gene may cause. There is currently no available treatment targeting diseases that result from both loss and gain of function mutations. NGGT uses dual-functional vectors to simultaneously remove harmful, mutated genes and replace them with normal, healthy genes to restore cellular function. We spoke to Guang Qu, chief operating officer and co-founder of NGGT, about the company's approach to gene therapies, how it is leveraging its platform technologies to cost-effectively accelerate development of these therapies, and the pipeline it is building.

Allison Freedman was an avid hiker, mother of young twins, and had just completed an MBA when she began suffering from severe back and rib pain and overwhelming fatigue. Repeated visits to the doctor and medical testing left her without a diagnosis. As her pain worsened, imaging revealed she had multiple broken ribs and vertebrae. At 42, a bone marrow biopsy confirmed that she had the blood cancer multiple myeloma. Freedman underwent intensive treatment including chemotherapy and a stem cell transplant. At one point she became bedridden. Though she went into remission, she had been unable to live the active lifestyle she previously enjoyed and took to physical therapy to build back her strength and regain her abilities. At 51, she managed to climb Mount Kilimanjaro in Tanzania and now mentors others with multiple myeloma. We spoke to Freedman about her journey through diagnosis and treatment, her recovery, and why she went from not wanting to talk about her condition to being a patient advocate.

Despite advancements in genetic testing, people with rare diseases often face a prolonged diagnostic odyssey involving multiple physician visits and misdiagnoses. Genetic testing company GeneDX is working to shorten the path to a diagnosis by expanding access to sequencing, collaborating with researchers, and accumulating data to better understand gene-disease relationships. We spoke to Katherine Stueland, CEO of GeneDx, about the state of genetic testing, what its 2022 acquisition by the AI-drive genomics company SEMA4 has meant to it, and what she thinks it will take to make meaningful change to the diagnostic odyssey.

Standard exome sequencing, which maps the protein coding regions of the genome, will deliver a diagnosis of someone with a rare disease in about 35 percent of cases. Ambry Genetics' ExomeReveal seeks to improve the diagnostic yield of these tests by adding RNA analysis to exome testing. That can help resolve variants of uncertain significance in about 2 to 3 percent of the cases. Ambry will also perform continuous reanalysis of the results over time to take into account new gene-disease relationships as they are discovered. This provides a diagnosis to about 5 percent of those without an answer. We spoke to Brigette Tippin Davis, chief operating officer for Ambry Genetics, about the diagnostic odyssey for people with a rare disease, Ambry's new ExomeReveal test, and what people can do to accelerate their path to a diagnosis.

Monica Coenraads, the mother of a daughter with Rett Syndrome, has played a critical role in catalyzing development of therapies to treat the rare, neurological disease. She co-founded and served as director of research for the Rett Syndrome Research Foundation. She later founded and today serves as CEO of the Rett Syndrome Research Trust. Her work shows how patient organizations can bridge the translational divide and de-risk rare disease drug development for biopharmaceutical companies. We spoke to Coenraads about her experience with Rett syndrome as a mother of a daughter with the condition, how she crafted a scientific agenda for the organizations she founded, and what other rare disease organizations can learn from her experience.

Earlier this year, the company gained attention when it reported that developed a customized antisense oligonucleotide to treat a boy with an ultra-rare neurodevelopmental disorder in a year's time. The company is leveraging AI to develop oligonucleotide medicines on demand. We spoke to Chris Hart, co-founder, president and CEO of Creyon Bio; about the proof-of-concept achieved with its recent N-of-1 therapy, the business model for Creyon, and the potential for its approach to reduce the time and cost of drug development.

When Yiwei She's son Leo was diagnosed with a severe neurodevelopmental condition, he was one of only two people known to have the ultra-rare disease. In a year, though, working with Creyon Bio, the family was able to move from the start of research for an ASO to treating Leo with the experimental therapy. We spoke to She, founder of the TNPO2 Foundation, about how her family was able to treat her son Leo with an experimental ASO with relative speed, the work the TNPO2 Foundation is doing to accelerate the diagnosis of other children with ultra-rare conditions, and its efforts to find accessible and affordable pathways to treatments for others.

Rare disease patient organizations are increasingly driving the discovery and development of therapies to treat the conditions on which they are focused. Organizations are seeking ways to accelerate these programs and advance them to the point where a biopharmaceutical partner might be willing to take them over. DevineBio was created to partner with patient organizations and provide them with the capability to discover and develop therapies and advance them to the clinic. We spoke to Chris Hopkins, CEO of DevineBio, about how the company works with patient organizations, how far it will advance programs, and its exit strategy.

Gene therapies have emerged as an important and growing area of medicine, but various players in the healthcare continuum are trying to understand the unique development, regulatory, and other issues surrounding this emerging modality. Avery McIntosh and Alex Sverdlov, both biostatisticians, have edited the new book “Development of Gene Therapies: Strategic, Scientific, Regulatory, and Access Considerations,” a reflection of their efforts to understand the complex of considerations the advent of these therapies raise. We spoke to McIntosh, director at Pfizer, and Sverdlov, senior director of statistical analysis at Novartis, about their new book, how a pair of biostatisticians view the challenges of gene therapy development, and why these therapies don't easily fit into existing models.

Siblings and children of people with the rare, neurodegenerative disease amyotrophic lateral sclerosis are being offered a test in the United Kingdom at no-cost to see if they carry mutations to one of more than 40 genes that would make it likely for them to develop the condition. Sano Genetics developed the test under a grant from Innovate UK. The hope is the effort will expand the understanding of the condition while allowing people who are likely to develop the disease to make informed decisions about their lives. We spoke to Paul Wicks, vice president of neuroscience for Sano, about its test for ALS-related gene mutations, how it works, and why some healthy people might want to take advantage of it.

Multiple sulfatase deficiency is a rare and progressive neurodegenerative disease. The patient advocacy organization United MSD Foundation has been able to advance a gene therapy into preclinical development for the ultra-rare condition through modest investment by pursuing a focused research strategy and leveraging partnerships. In May 2023, The Bespoke Gene Therapy Consortium, the National Institutes of Health-led public-private partnership selected the program for its clinical trial portfolio and will fund a phase 1/2 clinical trial for the therapy. We spoke to United MSD Foundation Executive Director Sarah Cortell Vandryspen, and UT Southwestern Gene Therapy Core Director Steven Gray. about United MSD Foundation's research strategy, what enabled it to advance a gene therapy as fast as it did, and what other patient organizations can learn from its success.

Despite the growing demand for genomic data and the falling price of genome sequencing, costs continue to restrain its use. Single Technologies, which is developing a three-dimensional approach to sequencing, believes it can cut the cost to just $10 per genome for consumables. That's a drop from estimates of about $600 today. We spoke to Johan Strömqvist, CEO and founder of Single Technologies and Bob Kain, advisor to the company, about its 3-D Sequencing, how it works, and how this can open up expansive use of the technology.

Nonsense mutations prematurely end the translation of a gene into protein and can result in a serious deficiency. About 10 to 15 percent of inherited genetic diseases involve nonsense mutations. Alltrna is developing transfer RNA therapies designed to correct the problem in protein synthesis caused by these aberrations. What's particularly exciting about the approach is that a single therapy has the potential to work across nonsense mutations regardless of the gene in which they occur. We spoke to Michelle Werner, CEO of Alltrna, about nonsense mutations, how the company's transfer RNA therapies work, and why the approach has the potential to address so many diseases at once.

Effie Parks is well known in the rare disease community as both a patient advocate and host of the Once Upon a Gene podcast. Like many advocates, she was thrust into the world of rare diseases following the diagnosis of her son Ford with an ultra-rare neurodevelopmental disorder known as CTNNB1 syndrome. Recently she published a map of the journey that a family undergoes when seeking a diagnosis a rare disease, a humorous answer to the orderly way organizations typically portray the experience. We spoke to Parks about her experience with the diagnostic odyssey for her son Ford, her version of the map to a genetic diagnosis, and what organizations usually get wrong. Click here to view the map.

Inherited retinal diseases are a group of genetic conditions that cause progressive and severe vision loss, such as retinitis pigmentosa, choroideremia, and Stargardt disease. Though they vary in terms of their genetic drivers, they are characterized by degeneration of photoreceptor cells in the retina. Collectively, inherited retinal diseases affect more than 2 million people around the world and are largely without reliable treatment options. Kiora Pharmaceuticals is developing a new class of therapies that can restore vision in these conditions by targeting retinal ganglion cells and enabling them to become light sensing to compensate for the degeneration of rods and cones in the eye. We spoke to Brian Strem, CEO of Kiora Pharmaceuticals, about inherited retinal diseases, how Kiora's experimental therapy works to treat these conditions, and a recent collaboration that will help drive clinical development of its lead experimental therapy.

For people in rural communities, access to genomic testing can require getting on a waitlist, delays in clinical assessment, and multiple visits to urban medical centers. A pilot study from Children's Mercy Research Institute in Kansas City, Missouri, found that by partnering with a rural clinic in a direct-to-provider model it was able to more than double the historic rate for rare disease diagnosis among the rural population and also cut the time-to-diagnosis by about five months. We spoke to Ana Cohen, assistant director of molecular genetics at CMRI, about its direct-to-provider model, how providing local support to patients at their regular clinics allowed them to bypass bottlenecks, and how the approach can shorten the time to a diagnosis for people with rare diseases in rural communities.

The cornea is a transparent and multi-layered dome that sits at the front of the eye. It not only provides protection, but bends light to focus it on the retina. Many corneal diseases cause scarring that reduces the transparency of the cornea and results in the loss of vision. In fact, corneal diseases are a leading cause of blindness. Claris Bio is seeking to address the need for therapies to treat corneal disease by developing recombinant human deleted hepatocyte growth factor to improve and accelerate corneal healing. We spoke to Clarke Atwell, CEO of Claris Bio, about the cornea, the role hepatocyte growth factor plays in its healing, and the rare and chronic condition neurotrophic keratitis that it is focusing on as its lead indication.

Lennox-Gastaut syndrome and Dravet syndrome are two rare, developmental and epileptic encephalopathies. Drug developers have sought to address epilepsies by altering the electrical activity in the brain. Ovid therapeutics, though, has taken a novel approach with its experimental therapy soticlestat by seeking to restore homeostasis to the brain. We spoke to Meg Alexander, chief strategy officer of Ovid, about rare epilepsies, how the company's experimental therapy soticlestat works, and the potential to apply the approach to other CNS conditions. Since recording this episode, there have been new results on soticlestat released. Ovid's partner Takeda this week reported that soticlestat narrowly missed its primary endpoint in its phase 3 Dravet syndrome study while showing clinically meaningful and nominally significant effects in multiple key secondary efficacy endpoints. It also missed its primary endpoint of reduction in major motor drop seizures as compared to placebo in a separate phase 3 study in Lennox-Gastaut syndrome. Takeda said it will be engaging with regulators to determine the best path forward.

Zevra Therapeutics, formerly KemPharm, rebranded itself in early 2023 following the acquisition of the experimental therapy arimoclomol for the rare lysosomal storage disorder Niemann-Pick type C. Zevra is Greek for “zebra,” a symbol of rare disease. The company subsequently built out its rare disease pipeline through the acquisition of Acer Therapeutics in November 2023. An FDA decision on arimoclomol is due by the end of September. We spoke to Neil McFarlane, president and CEO of Zevra Therapeutics, about Niemann-Pick type C disease, the FDA's upcoming decision on whether to approve the drug, and its broader efforts to build itself into a rare disease therapeutics company.