RARECast

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...

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...

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 again...

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 ran...

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 char...

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 signat...

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...

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 fi...

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 beha...

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...

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 f...

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...

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 tu...

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, th...

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 rep...

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 Foundat...

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 co...

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 th...

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 an...

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-qualit...

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, s...

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 selecti...

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 multi...

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...

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...