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 ...

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 har...

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...

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 gen...

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 Gr...

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 del...

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...

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 pro...

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 payloa...

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 se...

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 diagn...

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 com...

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. Al...

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 informat...

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 designe...

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 ...

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 m...

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 Gene...

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 tr...