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For people living with primary biliary cholangitis (PBC), the burden of disease can extend far beyond the liver. Debilitating fatigue, relentless itching, and other often-invisible symptoms can disrupt work, relationships, and daily routines, while misconceptions about liver disease add stigma to an already difficult experience. We spoke with Carol Roberts, president of the PBCers Organization, discusses her own experience with this rare autoimmune condition, what a recent patient survey reveals about its day-to-day toll, and how an evolving treatment landscape is changing expectations for care.

Susan Busch remembers her son Mike as sensitive, observant, and determined to do things that did not come easily to him. Born with the complex neurodevelopmental condition 22q11.2 deletion syndrome but not diagnosed until he was 13, Mike experienced medical emergencies, learning difficulties, and later severe psychiatric symptoms. For Busch, a nurse, raising him meant navigating healthcare and school systems while repeatedly questioning whether she was making the right choices. Busch, author of the 2013 Yearning for Normal, reflects on her son’s life, the isolation and self-doubt of caregiving, and what it means to love and support a child whose life doesn’t follow the path a parent imagined.

People with rare genetic diseases can spend years seeking a diagnosis, while researchers lack much of the detailed patient information needed to develop better diagnostic tools and treatments. Medical records capture only part of the picture, often leaving out observations, images, and videos that patients and caregivers can provide. Probably Genetic is addressing these gaps through a direct-to-patient platform that connects eligible patients with genetic testing and counseling while assembling clinical, genetic, and patient-reported data for research. Lukas Lange, co-founder and CEO of Probably Genetic, discusses the company’s approach, its ARPA-H-supported Project Rosetta, and how richer patient data could help shorten the diagnostic journey and lay the groundwork for new treatments.

For patients with rare diseases and other complex conditions, a prescription does not necessarily mean treatment can begin. Insurance approvals, fragmented communication, and confusing administrative requirements can leave patients and caregivers struggling to get the care their doctors recommend. Infinitus seeks to close that gap with an AI platform that automates conversations and coordinates information among patients, providers, pharmacies, insurers, and drugmakers—from benefits verification and prior authorization to treatment updates and ongoing patient support. Ankit Jain, co-founder and CEO of Infinitus, discusses how his daughter’s rare disease exposed the obstacles families face, how the company’s AI agents work to reduce delays, and where human judgment and connection must remain central to care.

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.

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.