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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.