RARECast

ALS is a rapidly progressive neurodegenerative disease in which the loss of motor neurons steadily erodes patients' ability to move, speak, and live independently. Available therapies have had limited impact on disease progression. Coya Therapeutics is pursuing an immune-based approach built around restoring the function of regulatory T cells. Its experimental therapy, COYA 302, combines the cytokine IL-2 with CTLA4-Ig, a fusion protein that dampens inflammatory myeloid-cell activity. Arun Swaminathan, CEO of Coya, discusses how dysfunctional regulatory T cells contribute to neuroinflammation and neuronal damage in ALS, why the company is targeting them as a driver of disease progression, and the case for its dual immunomodulatory approach.

After unexplained facial and neck pain escalated into debilitating migraines and widespread symptoms, Monica Dubeau spent 20 months navigating 111 medical appointments with 26 specialists across four states and two countries before receiving a diagnosis of craniocervical instability. Further evaluation revealed Chiari malformation, tethered cord syndrome, and hypermobile Ehlers-Danlos syndrome—a connective-tissue disorder that she says helped explain a constellation of problems previously treated separately. Drawing on her career in governance, risk, and audit, Dubeau approached her medical journey as an investigation, tracking symptoms, test results, care providers, and patterns across health systems. Dubeau, patient advocate and founder of YouMightBeAZebra.com, discusses how her professional background helped her investigate her own case; why she views brief clinical visits and fragmented care as systemic failures; and what health systems, insurers, clinicians, and policymakers could do to shorten the road to a diagnosis for people with rare diseases.

For people with ultra-rare genetic diseases, a diagnosis can come with a devastating realization that there may be no treatment in development because the patient population is too small to attract traditional biopharma investment. Nome is working to change that by combining patient-led drug development with AI-enabled scientific and operational support. Steven Ringel, founder and CEO of Nome and founder of the Kizuna Foundation, discusses how the company is helping families and patient organizations identify viable genetic-medicine options, build development plans, and find qualified partners who can help advance individualized therapies toward the clinic.

Genetic medicine has already begun to transform the treatment of some inherited diseases, but the brain remains one of its most formidable frontiers. For disorders such as Huntington’s disease and ALS, scientists may understand key genetic contributors and have increasingly powerful editing tools, yet getting those tools safely, efficiently, and selectively into vulnerable neurons is another matter entirely. Evox Therapeutics is developing an approach built around naturally occurring nanoparticles that cells use to communicate, known as exosomes, as delivery vehicles for CRISPR-based medicines. We spoke with Per Lundin, the company’s co-founder and CEO, about the promise and limitations of exosome-enabled gene editing, how the company is prioritizing its pipeline, and what it will take to establish this emerging therapeutic strategy in the clinic.

Kleefstra syndrome is a rare neurodevelopmental condition with significant unmet medical needs, but a growing understanding of its underlying biology is creating new opportunities for therapeutic development. Eric Scheeff, chief scientific officer of Idefine and parent of a child with Kleefstra syndrome, discusses the organization’s progress in building the scientific foundation for a potential treatment, the role of its patient community, and the work ahead to translate scientific insights into meaningful therapies.