RARECast

Congenital hyperinsulinism can turn a newborn’s first days into a medical emergency. The body produces too much insulin, blood sugar can fall to dangerous levels, and every delay in diagnosis or lapse in control can put the developing brain at risk. Even when children survive and receive expert care, families may spend years managing feeding schedules, glucose checks, medications and hospitalizations. In some cases, children undergo life-altering pancreatic surgery that can create new medical challenges. Julie Raskin, CEO of Congenital Hyperinsulinism International, discusses how her family’s experience with the condition led her to build a global, patient-driven effort to advance new treatments, how the organization has forged partnerships with industry to do that, and how it is working to improve the lives of people living with the disease.

Guillain-Barré syndrome is a rare, rapidly progressive autoimmune disorder in which harmful inflammation attacks peripheral nerves, potentially causing acute paralysis, respiratory failure, and lasting disability. Annexon is developing tanruperbart, a single-infusion monoclonal antibody designed to block C1q, the initiator of the classical complement pathway. By inhibiting C1q early in GBS, Annexon believes it can interrupt the harmful inflammatory cascade before it causes further peripheral nerve damage. Doug Love, CEO of Annexon, discusses the biological role of the classical complement pathway in Guillain-Barré syndrome, the limitations of current nonspecific standards of care, and the company’s effort to bring a targeted monoclonal antibody designed to rapidly halt the inflammatory cascade in patients with this condition.

People with the rare genetic condition Gorlin syndrome can develop dozens or even hundreds of basal cell carcinomas over their lifetimes, often requiring repeated surgeries that carry physical, emotional, and financial consequences. Medicus Pharma is developing SkinJect, an experimental microneedle patch designed to deliver microdoses of the chemotherapy drug doxorubicin directly into basal cell carcinoma lesions. Raza Bokhari, CEO of Medicus Pharma, discusses the company’s approach to developing a localized, non-surgical treatment for people with Gorlin syndrome, how the patch is intended to induce tumor-cell death while limiting systemic exposure, and the platform’s potential applications beyond Gorlin syndrome.

Sickle cell disease is caused by a single mutation in the beta-globin gene that leads to painful crises, anemia, and organ damage. Despite advances in treatment, it remains a devastating and often overlooked global health challenge, particularly in low-resource settings where children frequently go undiagnosed until life-threatening complications arise. The PERICLES project is an ambitious research initiative exploring prenatal gene editing to correct sickle cell disease before birth by targeting fetal blood-forming stem cells. Panicos Shangaris, a clinical senior lecturer and consultant in maternal and fetal medicine at King’s College London, discusses what daily life looks like for people living with sickle cell disease today, the limits of existing therapies, and why treating the condition in utero could offer families a one-time, potentially curative therapy to prevent the disease before symptoms appear.

Many older adults may dismiss dropping objects, struggling with stairs, or tiring on short walks as a matter of just getting older, but it can be an early sign of a serious group of disorders known as late-onset neuromuscular diseases (LONDs). The American Neuromuscular Foundation’s Why Behind Your Weakness campaign seeks to raise awareness of LONDs and the shared symptom patterns that too often go unrecognized. Myasthenia Gravis Association Executive Director Allison Foss and Director of the Neuromuscular Center at Cleveland Clinic John Morren discuss the everyday impact of conditions like myasthenia gravis, ALS, CIDP, and limb-girdle muscular dystrophies; why unexplained, progressive weakness deserves a closer look; and how a new clinical decision support tool can help primary care providers distinguish age-related changes from true neuromuscular red flags.

Chiesi Global Rare Diseases has rapidly evolved from a small, regional rare‑disease business into a global organization, leveraging strategic deals and development bets to reshape standards of care for patients worldwide. Giacomo Chiesi, head of the unit, discusses how the business has grown through acquisitions, its move into CRISPR gene editing and blood–brain barrier‑crossing enzyme platforms, and its broader vision of delivering meaningful quality‑of‑life improvements for people living with rare diseases.

When Tom Sayiner was diagnosed with the fatal neurodegenerative disease ALS, he and his wife, Tamara, learned that tofersen had been approved in Europe as a therapy that could slow the progression of his genetic form of the disease. But the Sayiners, who live in Sweden, soon discovered they could not access the drug because a Swedish health technology assessment council determined there was insufficient data to demonstrate that the costly therapy provides a clear benefit. Instead, they are working to raise funds to purchase the drug in Germany, while Tom has also enrolled in a clinical trial in hopes of accessing a potentially beneficial therapy. The Sayiners discuss the gap between regulatory approval and real-world access in Sweden, the steps they have taken to explore cross-border care; and how geography, cost, and policy can be as life-limiting as the disease itself.

People with rare, severe autoimmune diseases often live for years with progressive, disabling conditions managed by chronic immunosuppression that rarely addresses the underlying cause. Kyverna is developing an autologous CAR T-cell therapy designed to deliver a deep immune reset by broadly depleting pathogenic B cells, followed by repopulation with naïve, non-pathogenic B cells and normalization of T-cell function and cytokine profiles. This approach has the potential to enable durable remissions and discontinuation of background immunosuppressive therapies after a single infusion. The company’s pipeline is focused on neuroimmunology, with lead programs in generalized myasthenia gravis and stiff person syndrome. Warner Biddle, CEO of Kyverna Therapeutics, discusses the company’s B cell–targeting cell therapy platform, the range of autoimmune diseases it aims to address, and its next-generation therapies in development.

The case of baby KJ Muldoon, an infant born with a lethal genetic metabolic disorder, demonstrates the potential to compress years of therapeutic development into months using an in vivo base editing approach. Jeff Coller, director of the Johns Hopkins RNA Innovation Center, wrote about the case in a New York Times op-ed, arguing that CRISPR-based base editors—delivered via lipid nanoparticles as mRNA molecular surgery payloads—could be generalized to thousands of monogenic disorders. He further explains that realizing this promise will be constrained less by scientific limitations than by regulatory, manufacturing, and reimbursement challenges. Coller also outlines what it will take to make bespoke therapies economically and operationally viable, and argues that failure to scale this approach would reflect not a failure of science, but of imagination.

Families seeking a diagnosis for a rare disease often face a protracted diagnostic odyssey that can include ER visits, specialist referrals, and dead ends, even at world-class medical centers. Parents bounce from doctor to doctor while payers absorb mounting costs, and the pivotal moment of putting a name to a disease—which can reduce unnecessary care and emotional distress—arrives late, if at all. Sunstone Health is seeking to industrialize the path to answers by using AI to scan claims data for patterns that flag likely genetic disease, recruiting high-risk families, and fast-tracking whole-genome sequencing through a top clinical lab. Sunstone Health founder Joshua Resnikoff discusses how his son’s rare disease diagnostic odyssey gave rise to the company, how Sunstone is working to transform the path to a diagnosis, and its business model of relying on the savings it delivers to self-funded employers.

Erythropoietic protoporphyria (EPP) is a rare, inherited metabolic disorder that triggers a toxic photochemical reaction in skin when exposed to light. A short time in the sun for someone with the condition can result in excruciating, second-degree–like burns and leaves patients sidelined from normal outdoor activity. Craig Leppert, who has EPP, saw his childhood shaped by constant vigilance against sunlight, years-long diagnostic delay, and the social isolation of a condition few clinicians recognize. Leppert, founder of the non-profit Shadow Jumpers, discusses his experience with EPP, the benefits he’s had as a participant in a clinical trial of an experimental therapy to treat the condition, and the potential for transforming what’s possible for people living with the disorder.

Many disease‑causing genes are too large to be packaged into standard AAV gene therapy vectors, leaving a long list of otherwise gene-therapy-ready conditions without viable treatments. SpliceBio is leveraging a protein splicing platform based on engineered split inteins to overcome the cargo limitations of AAV gene therapy vectors, enabling delivery of large genes to potentially treat a broad range of monogenic conditions. The company’s lead program is a dual AAV gene replacement therapy to treat Stargardt disease, a rare inherited condition that causes progressive vision loss. Miquel Vila-Perello, CEO of SpliceBio, discusses the company’s platform technology that enable to the delivery of large genes in AAV vectors, its work to date in Stargardt disease, and preclinical data across more than 20 large-gene targets supporting its platforms use in ophthalmology and CNS indications.

Multiple system atrophy is a rapidly progressive neurodegenerative condition that is often misdiagnosed as Parkinson’s disease but carries a far grimmer prognosis. MSA has a median survival of just seven to eight years after symptom onset. Toxic aggregates of alpha‑synuclein and excess brain iron create a vicious cycle of neuronal damage that drives the multisystem motor and autonomic decline characteristic of the disease. Alterity Therapeutics is developing an oral, brain‑penetrant therapy designed to redistribute excess iron, reduce alpha‑synuclein aggregation and oxidative injury, and ultimately slow disease progression. David Stamler, CEO of Alterity, discusses the biology of MSA, the company’s promising clinical results to date, and why this therapeutic approach may also have application in other neurodegenerative diseases.

The ability to diagnose rare diseases is at a turning point as greater genomic awareness, technological advances in long-read HiFi sequencing, and improved economics are converging to shorten the diagnostic odyssey for patients and families. PacBio’s long-read whole-genome sequencing overcomes the limitations of exomes and short read technologies by capturing structural variants, epigenetic signatures, and regulatory information, which raises diagnostic yields by 10 to 15 percentage points and increasingly justifies its use as a first-line test. PacBio CEO Christian Henry discusses the company’s long-read HiFi whole-genome sequencing, how it is reshaping the rare disease diagnostic journey, and the growing acceptance of the technology among payers.

Friedreich’s ataxia is a progressive, multisystem disease that robs people of coordination, independence, and often life itself. Until recently, there had been no approved therapies. In Friedreich’s ataxia, a genetic mutation causes a deficiency in frataxin, a protein that plays an essential role within mitochondria and affects enzymes involved in energy production. Solid Biosciences is developing a gene therapy designed to restore frataxin where it is needed. Friedreich’s Ataxia Research Alliance CEO Jennifer Farmer and Solid Biosciences chief medical officer Gabriel Brooks discuss the lived reality of Friedreich’s ataxia, Solid Bioscience’s next-generation gene therapy now in development to address the underlying cause of the disorder, and what genuine partnerships between patient organizations and industry look like when patient priorities drive trial design and development decisions.

When Kasey Walsh's daughter was diagnosed with an ultra-rare genetic disorder, she discovered a frustrating paradox: researchers desperately needed insights from patient families, yet institutional barriers made it nearly impossible to capture the nuanced, lived experiences that could inform drug development and improve care. Drawing on her background as a healthcare service coordinator and her firsthand experience navigating rare disease research, Walsh created Winsights, a platform that transforms casual patient conversations into structured, regulatory-grade data while ensuring families retain ownership and control over how their contributions are used. Walsh, founder and CEO of Winsights, discusses her daughter's diagnostic journey, the critical gaps in how patient experience informs drug development, and how Winsights empowers rare disease communities to drive research priorities.

Patients facing medical decisions often find themselves drowning in confusing information that is laden with scientific terminology and often neglects the human element. Keith Berelowitz, a clinical research operations veteran motivated by personal experience, created the Trialport platform to embed trial information in patient community websites with plain language, multilingual support, and behavioral assessments that go beyond medical eligibility. The company partners with patient advocacy groups while providing sponsors with real-time behavioral insights that reveal how patients engage with trial information. Berelowitz, founder and CEO of Trialport, discusses his vision for a future where clinical trials are discussed alongside standard of care as a routine healthcare option, the gap between clinical trial availability and patient awareness, and how the Trialport platform works to help both patients and sponsors understand readiness for clinical trials.

Matching phenotype to genotype at scale could transform how rare diseases are found, understood, and treated. Komodo Health has partnered with GeneDx to build one of the most comprehensive longitudinal rare disease datasets ever assembled. John Wollman, head of revenue strategy at Komodo Health, discusses how Komodo’s longitudinal real‑world data on more than 330 million de-identified U.S. patient journeys, combined with GeneDx’s genomic testing and rich phenotypic information, can shorten diagnostic odysseys, rapidly enable natural history studies, and help stakeholders across the rare disease continuum make smarter and faster decisions for people living with rare diseases.

Whole genome sequencing is reshaping the rare disease diagnostic odyssey by replacing years of serial, narrow gene panels and helping patients with suspected rare diseases obtain faster, more definitive answers. Akash Kumar, co‑founder and chief medical officer of MyOme, discusses where genome sequencing now fits into care pathways, how it captures hard‑to‑detect variant types; and what it means for treatment decisions, clinical trial access, and the emotional burden on families searching for a diagnosis.

Nicole Johnson and Nasha Fitter are both mothers of daughters with the ultra-rare neurodevelopmental condition FOXG1 syndrome, which currently has no approved disease-modifying therapies. The disorder causes profound developmental disabilities, epilepsy, motor and speech impairments, and multi-system challenges. The two mothers co-founded the FOXG1 Research Foundation to advance treatments for the condtion. Johnson and Fitter discuss how a parent-driven foundation became a virtual biotech capable of advancing a gene therapy into human clinical trials, how they prioritized translational work over academic projects that don’t move a therapy toward the clinic, and the lessons they’ve learned that can guide other rare disease communities.

When Jim Foote lost his son, Trey, to osteosarcoma, it exposed the limits of one-size-fits-all cancer protocols. He co-founded First Ascent Biomedical to apply functional precision medicine to rare and pediatric cancers. First Ascent uses this approach to transform care for children with rare and relapsed cancers by moving beyond protocols built on averages to decisions grounded in each child’s tumor biology. Foote, CEO of First Ascent, discusses how combining genomics, functional assays, and AI offers a realistic path to better outcomes, fewer lifelong toxicities, and more rational use of existing anti-cancer drugs that are not yet used optimally for individual children.

When the immune system misfires, it can cause very different rare diseases that, on the surface, don’t seem related at all. Sanofi, though, is exploring similarities in rare autoimmune conditions that may allow it to treat a number of different disorders with a single therapy. We spoke to Pablo Sardi, head of rare disease research at Sanofi, about the company’s oral BTK inhibitor rilzabrutinib, the challenges of testing one drug in different rare diseases, and how this kind of approach might push doctors to focus less on symptoms and more on the root causes of a rare disease.

Špela Miroševič, a psychotherapist and biopsychologist working as a researcher at the Medical University Ljubljana in Slovenia became immersed in rare disease drug development after the birth of her son Urban. As an infant, Urban was diagnosed with the ultra-rare, neurodevelopmental condition CTNNB1 syndrome. Miroševič founded the CTNNB1 Foundation, which is now advancing Urbagen, an AAV9 gene replacement therapy named for her son. We spoke to Miroševič about how she assembled an international team of researchers, raised millions of dollars to fund research and development, and what it took to push a parent-led gene therapy all the way into a first-in-human clinical trial.

Schaaf-Yang syndrome is an ultra-rare neurodevelopmental disorder that is closely related to but distinct from Prader-Willi syndrome. It typically presents from birth with poor muscle tone, feeding and breathing difficulties, and later evolves into a broad spectrum of more severe developmental delay, intellectual disability, autism, endocrine dysfunction, and disruptive sleep patterns. The Foundation for Prader-Willi Research’s GeneSYS initiative is leveraging antisense oligonucleotide technology to knock down the toxic truncated protein underlying Schaaf-Yang, orchestrating collaborations with academic scientists, contract research organizations, and patient families to move from cell and animal models toward first-in-human studies. We spoke to Theresa Strong, director of research programs for the Foundation for Prader-Willi Research, about the challenges of delivering therapy to the hypothalamus, navigating ultra-rare drug economics, and how patient-led organizations can drive sophisticated translational programs for conditions that affect only a few hundred people worldwide.

Polycythemia vera is a chronic blood cancer in which bone marrow stem cells acquire mutations that drive uncontrolled production of red blood cells and other lineages, thickening the blood and causing fatigue, brain fog, and intense itching when in contact with water. The condition also raises the risk of dangerous blood clots. Current management relies on removing blood to lower red blood cell counts, using aspirin, and prescribing drugs to reduce blood cell production, all of which can be burdensome. We spoke with hematologist‑oncologist Marina Kremyanskaya and PV patient advocate Nona Baker about polycythemia vera, how it reshapes everyday life for patients and families, and the promise of new therapies in development.

Families of children with the ultra-rare mitochondrial disorder pyruvate dehydrogenase complex deficiency, or PDCD, are fighting to get the U.S. Food and Drug Administration to provide a path to approval Saol Therapeutics’ experimental therapy without requiring another trial. The agency refused to approve its therapy late last year, despite gains in survival, biomarkers, and real‑world function that parents say the trial missed. We spoke with Hope for PDCD Founder and CEO Frances Pimentel and parent board member Kim Higbee about the community’s reaction, the gap between patient experience and study endpoints, and the struggle to get regulators to align their actions with their stated commitments to ultra‑rare disease patients.

Rett syndrome is a rare neurodevelopmental disorder that disrupts a child’s ability to purposely use their hands, communicate, and move around. It creates a lifelong caregiving burden for families, and there are still no treatments that truly change the course of the disease. Neurogene is developing a one-time gene therapy that has shown promising early results, with children gaining new skills and continuing to make developmental progress over time. We spoke with Rachel McMinn, CEO of Neurogene, about Rett syndrome, the company’s technology for controlling gene expression, and the encouraging data they’ve seen so far.

Rare diseases are often thought about in terms of the financial burden they create, but a new paper from the World Economic Forum urges policymakers, payers, and business leaders to see them as one of the greatest underappreciated opportunities in global health. In “Making Rare Diseases Count: How Better Data Can Unlock a Multi-Trillion Dollar Opportunity,” the organization argues that high-quality, patient-centered data must sit at the core of any rare disease strategy. We spoke to Will Greene, lead author of the paper and a board member of the Foundation for Prader-Willi Research, about the need for smarter collection, sharing, and analysis of data; how doing so can unlock outsized returns in human health, and what it will take to mobilize a broad set of stakeholders around that vision.

A single genetic diagnosis can ripple through generations and reshape medical care for an entire family. Cascade genetic testing, the offering of targeted genetic testing to biological relatives of a person in whom a disease-causing variant has already been identified, can find at‑risk relatives, improve outcomes, and save costs through early treatment and prevention. We spoke with Rajani Aatre, senior genetic counselor at Michigan Medicine’s Frankel Cardiovascular Center, about the importance of cascade genetic testing, the ethical tension between honoring a patient’s privacy and protecting relatives from preventable harm; and the question of whether, when, and how to share life‑changing genetic information with relatives.

Autoimmune diseases like myasthenia gravis have long forced patients to trade daily function for chronic immunosuppression, but Cartesian Therapeutics is betting that its experimental RNA‑engineered CAR T cells can rewrite that equation. The company’s lead experimental therapy, Descartes‑08, is designed to deliver deep, durable remissions through a short course of outpatient infusions that selectively eliminate the plasma cells driving disease, while sidestepping the toxicity and logistical hurdles of conventional DNA‑based CAR T therapies. We spoke to Carsten Brunn, CEO of Cartesian Therapeutics, about how the company’s RNA‑engineered CAR T cells target the root cause of autoimmune diseases, data from its phase 2 study in myasthenia gravis, and the potential to expand the approach into myositis and other rare autoimmune indications.

Drug development has long been a costly, trial-and-error effort, with nine out of ten clinical programs failing despite major scientific advances. One reason is that biological information remains fragmented in silos, and traditional R&D approaches often rely on narrow, task-specific datasets. Bioptimus aims to change this by using AI to build a foundation model that integrates multimodal, multiscale biological data into a single body of knowledge. The approach has particular promise for rare diseases, where patient numbers and data are scarce, preclinical models are poor, and development economics are challenging. We spoke with Jean-Philippe Vert, co-founder and CEO of Bioptimus, about the inherent messiness of biology, the potential to transform rare disease drug development with a foundation model, and how uncovering similarities between conditions could enable repurposing of existing drugs.

Shimon Sakaguchi shared the 2025 Nobel Prize in Physiology or Medicine for his identification of regulatory T cells that suppress autoimmune responses. His work laid the foundation for RegCell, a company he co-founded to develop cell therapies that provide targeted treatments for autoimmune disease without compromising healthy immune function. RegCell epigenetically reprograms patient T cells into regulatory T cells. We spoke to Michael McCullar, CEO of RegCell, about the role of dysfunctional Tregs in autoimmune diseases, the firm’s use of epigenetically modified regulatory T cells to treat these conditions, and how this approach can selectively suppress harmful immune responses without causing broad immunosuppression.

When a toddler with a neurodevelopmental delay, poor muscle tone, and no hair came to Caleb Bupp’s genetics clinic, it led not only to the discovery of a new, ultra-rare disease, but the identification of a potential treatment in DFMO, a drug long used to treat a chronic parasitic disease. Bupp is now collaborating with others including Every Cure, a nonprofit biotech working to expand the use of repurposed drugs. While a number of patients have begun using the drug, the U.S. Food and Drug Administration has urged the group to move forward with a clinical trial. We spoke to Bupp, pediatric geneticist at Corewell Health Helen DeVos Children’s Hospital in Grand Rapids, Michigan, about the discovery of the condition known as Bachmann-Bupp syndrome, how he and his colleagues identified a potential treatment in an existing drug, and the path forward.

Amber Freed transformed the shock of her son’s diagnosis with an ultra-rare neurodevelopmental disorder into a determined campaign for gene therapy. With no clinical roadmap, sparse literature, and doctors offering only symptomatic care, she taught herself biology basics, established a nonprofit, and assembled a scientific team. She focused on gene replacement therapy as the most viable path, and son became the first patient treated in a clinical trial of the experimental gene therapy last September. We spoke to Freed, founder and CEO of SLC6A1 Connect, about how a parent with no scientific background catalyzed the development of the first experimental gene therapy for SLC6A1-related disorder, mobilized scientists, and what other rare disease communities can learn from her journey.

Tuberous sclerosis complex is a rare genetic condition caused by changes in the TSC1 or TSC2 gene that over-activate a key growth-control pathway, known as mTOR. This leads to seizures that often don’t respond to existing medicines and to noncancerous tumors in organs such as the brain, kidneys, lungs, and skin. In fact, more than 65 percent of people with TSC-related epilepsy still have seizures despite available treatments. Though mTOR inhibitors can help some patients, their benefits are limited because of side effects due to their lack of specificity. Aeovian Pharmaceuticals is developing an experimental therapy that precisely targets the overactive part of this pathway and avoids the part thought to cause many side effects. We spoke to Allison Hulme, CEO of Aeovian Pharmaceuticals, about tuberous sclerosis complex, the problems with existing therapies for seizures related to the condition, and the opportunity for its next-generation, selective mTOR inhibitors to treat tuberous sclerosis complex and beyond.    

​The Oxford-Harrington Rare Disease Centre represents a transatlantic alliance created to bridge academic research and drug development for rare diseases. Founded in 2019 by the United Kingdom’s University of Oxford and the Cleveland-based Harrington Discovery Institute, the center leverages Oxford's world-class rare disease research and Harrington's pharmaceutical-scale expertise to address translational challenges and advance promising therapies for rare diseases lacking approved treatments. We spoke to Matthew Wood, director of the Oxford-Harrington Rare Disease Centre, about the challenges of rare disease drug development, the resources the center brings to address them, and the mechanisms it has established to accelerate therapeutic development.

Floyd Stewart was diagnosed with late-stage nasopharyngeal carcinoma, a rare, fast‑growing head and neck cancer that advanced quietly until it appeared as a bulge in his neck. The diagnosis became a struggle for his entire family as his treatments reshaped family life for Floyd, his wife Monique, and their four children. We spoke to the Stewarts about how they navigated the healthcare system, the strain the experience put on their family, and why today they are rare disease advocates seeking to raise awareness for the rare cancer and help other families dealing with similar problems. 

There have been great advances in the treatment of cystic fibrosis, but nevertheless it remains a progressive, life‑shortening genetic disease as many patients still don’t reach normal function and continue to face infections, exacerbations, and impaired quality of life. Siona Therapeutics is building a new generation of small‑molecule therapies that directly stabilize the region most affected by the most common mutation underlying the disease for the roughly 90 percent of patients who carry the defect. We spoke to Mike Cloonan, CEO of Sionna, about its experimental therapy that stabilizes the misfolded protein at the heart of the disease, its exploration of combinations with existing and proprietary therapies, and its $219 million IPO in February, despite the difficult financing environment for development-stage biotechs.

As a college student, Megan Beaulieu first noticed her smile faltering and her arms growing weak, which she chalked up to stress and exhaustion. Within weeks, her symptoms had worsened to the point that she could no longer lift her hands to wash her hair—a progression that led to her diagnosis of myasthenia gravis, a rare autoimmune neuromuscular disease. Since then, she has taken to TikTok to share her journey. We spoke with Beaulieu, who now works as a project manager at a construction firm, about living with myasthenia gravis, her decision to use social media to educate and inspire others with the condition, and how she learned to advocate for herself before advocating for others.

Dermatomyositis is a rare multi-organ autoimmune condition that primarily affects the skin and muscles. It causes fatigue, muscle weakness, and painful skin rashes. Treatment for the condition has long centered on the use of chronic systemic steroids, which can carry long‑term toxicity. Priovant is developing brepocitinib, a dual TYK2/JAK1 inhibitor originally developed at Pfizer to treat the condition. We spoke to Ben Zimmer, CEO of Priovant, about the company's experimental targeted therapy to treat dermatomyositis, how its relationship with its parent Roivant frees it from reliance on the capital markets, and the broader potential of n the treatment.

Veteran biotech investors Steven St. Peter and Luke Evnin launched Vie Ventures to bridge traditional venture capital with disease-focused philanthropy to target autoimmune and immune-mediated diseases. The fund partners with large patient organizations, such as the Lupus Research Alliance and Scleroderma Research Foundation, to invest in series B and C rounds in clinical-stage companies. We spoke to St. Peter, co-founder and managing director of Vie Ventures, about the firm’s investment model, its initial focus on immune-mediated diseases, and its work with major patient organizations.

When Nikki McIntosh’s son Miles was less than a year old, he was diagnosed with a form of the rare neuromuscular condition spinal muscular atrophy. Since then, she has needed to learn how to manage the complexities of her own life while managing Miles’ care, coordinating his providers; and navigating the medical, financial, and emotional aspects of raising a child with a rare disease. McIntosh has shares her experience in a book intended to help others new to the journey of caring for a child with a rare disease. We spoke to McIntosh, author of “Rare Mamas: Empowering Strategies for Navigating Your Child’s Rare Disease,” about her book, the medical, emotional, and logistical challenges faced by rare disease families; and the importance of making time for self-care.

Spinocerebellar ataxia is a group of inherited, heterogeneous neurodegenerative diseases affecting coordination, speech, and vision. There are currently no FDA approved therapies for the more than 50 known types of SCA​, but there is a growing pipeline of therapeutic candidates. We spoke to Andrew Rosen, CEO of the National Ataxia Foundation, about the challenges of developing therapies for spinocerebellar ataxia, the critical role of patient-led organizations in early-stage research and advocacy, and the recent surge of therapeutic activity targeting these neurodegenerative conditions.

A recent report from the health research network and real-world data platform TriNetX argues that by aggregating electronic health records, billing claims, and registry data across hundreds of healthcare sites makes it possible to study rare diseases more efficiently. Doing so could enable access to enough patient data to conduct meaningful research, which is often impossible through traditional clinical trials. We spoke to Jeff Brown, chief scientific officer of TriNetX, about how real-world data can address common challenges in rare disease research, the hurdles that need to be addressed, and how advances in AI could revolutionize rare disease research by using this data to identify patients and unlock insights.

Huntington’s disease is a rare, inherited neurodegenerative disorder caused by a type of genetic mutation known as a trinucleotide repeat expansion, which leads to the production of a toxic protein that causes progressive brain cell loss. Vico Therapeutics is developing an experimental antisense oligonucleotide to treat the condition. Because the therapy targets the repeat expansion itself, rather than a specific gene, it may have applications across a broader set of so-called polyglutamine diseases of which Huntington’s is one. We spoke to Prarthana Khanna, vice president of corporate business development and strategy for Vico, about Huntington's disease, the company’s experimental ASO to target the disease, and why it has the potential to address multiple neurological diseases. 

After Philippa Ward’s five-month-old son, Thomas, suffered infantile spasms, he was soon diagnosed with tuberous sclerosis complex—a rare genetic disorder that causes noncancerous tumors to form on various organs, including the brain. Thomas experiences near-daily seizures, cannot communicate verbally, and, due to delayed motor skills, often requires the use of a wheelchair. We spoke to Ward about her journey as the mother of a child diagnosed with tuberous sclerosis complex, the challenges posed by the condition’s complexities, and how she found both a community of support and her own voice as an advocate.

Partnerships between biopharmaceutical companies and patient organizations can play a critical role in improving access and outcomes for people with rare diseases. However, to do so, companies must listen to patient communities and address the unique challenges they face. We spoke to Laura Russo, U.S. patient engagement lead for Pfizer, discusses how the company’s patient-facing teams work to bridge health systems and patient communities, how they help people with rare diseases navigate the healthcare system, and how they improve access through customized approaches ranging from providing transportation to care for people with sickle cell disease to providing education and support to community health workers.

Hunter syndrome is caused by the body’s inability to produce a critical enzyme needed to break down cellular waste. The condition can cause damage to organs throughout the body as well as to the brain. A new generation of therapies in development, including a gene therapy currently under review by the U.S. Food and Drug Administration, that has the potential to address the neurological symptoms of the disease. Still, patient advocates have been frustrated by regulatory delays and are seeking to push the FDA and Congress to take action. We spoke with Kristin McKay, CEO of the Hunter syndrome patient advocacy organization Project Alive, about the need for new therapies, the importance of early detection, and the patient community’s concerns with regulatory delays in approving needed treatments. An editor’s note: Since recording this podcast, the FDA granted accelerated approval to Stealth Biotherapeutics’ Forzinity for Barth syndrome, which is referenced in the discussion.

Developmental and epileptic encephalopathies are a group of rare disorders that are characterized by frequent seizures that often don’t respond to existing medications. These are complex conditions that involve progressive cognitive and behavioral manifestations that can pose significant burdens on patients and their families. In both clinical practice and within the biopharmaceutical industry, there has been a tendency to focus on seizure control, while often overlooking the non-seizure burdens of developmental and epileptic encephalopathies. We spoke to Amelie Lothe, global medical community head for rare epilepsies at UCB, about the need to view these developmental and epileptic encephalopathies as complex neurodevelopmental conditions, the need to go beyond seizure frequency when it comes to clinical trial outcome measures, and what drug developers can do to improve their research focus to include broader patient and caregiver experiences.

Achondroplasia is the most common form of dwarfism. Beyond short stature, people living with achondroplasia can experience serious health complications, including compression of the brainstem and upper spinal cord due to impaired development of the skull. Tyra Biosciences is developing a next-generation medicine to precisely target FGFR3, an overactive growth factor that causes achondroplasia. We spoke to Todd Harris, CEO of Tyra Biosciences, about the company’s experimental once-daily, oral medicine for achondroplasia; what’s known about it from studies conducted to date, and why he believes it will offer competitive advantages over existing therapies.