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.

Tuberous sclerosis complex is a rare genetic condition caused by changes in the TSC1 or TSC2 gene that over-activate a key growth-control pathway, known as mTOR. This leads to seizures that often don’t respond to existing medicines and to noncancerous tumors in organs such as the brain, kidneys, lungs, and skin. In fact, more than 65 percent of people with TSC-related epilepsy still have seizures despite available treatments. Though mTOR inhibitors can help some patients, their benefits are limited because of side effects due to their lack of specificity. Aeovian Pharmaceuticals is developing an experimental therapy that precisely targets the overactive part of this pathway and avoids the part thought to cause many side effects. We spoke to Allison Hulme, CEO of Aeovian Pharmaceuticals, about tuberous sclerosis complex, the problems with existing therapies for seizures related to the condition, and the opportunity for its next-generation, selective mTOR inhibitors to treat tuberous sclerosis complex and beyond.    

​The Oxford-Harrington Rare Disease Centre represents a transatlantic alliance created to bridge academic research and drug development for rare diseases. Founded in 2019 by the United Kingdom’s University of Oxford and the Cleveland-based Harrington Discovery Institute, the center leverages Oxford's world-class rare disease research and Harrington's pharmaceutical-scale expertise to address translational challenges and advance promising therapies for rare diseases lacking approved treatments. We spoke to Matthew Wood, director of the Oxford-Harrington Rare Disease Centre, about the challenges of rare disease drug development, the resources the center brings to address them, and the mechanisms it has established to accelerate therapeutic development.

Floyd Stewart was diagnosed with late-stage nasopharyngeal carcinoma, a rare, fast‑growing head and neck cancer that advanced quietly until it appeared as a bulge in his neck. The diagnosis became a struggle for his entire family as his treatments reshaped family life for Floyd, his wife Monique, and their four children. We spoke to the Stewarts about how they navigated the healthcare system, the strain the experience put on their family, and why today they are rare disease advocates seeking to raise awareness for the rare cancer and help other families dealing with similar problems. 

There have been great advances in the treatment of cystic fibrosis, but nevertheless it remains a progressive, life‑shortening genetic disease as many patients still don’t reach normal function and continue to face infections, exacerbations, and impaired quality of life. Siona Therapeutics is building a new generation of small‑molecule therapies that directly stabilize the region most affected by the most common mutation underlying the disease for the roughly 90 percent of patients who carry the defect. We spoke to Mike Cloonan, CEO of Sionna, about its experimental therapy that stabilizes the misfolded protein at the heart of the disease, its exploration of combinations with existing and proprietary therapies, and its $219 million IPO in February, despite the difficult financing environment for development-stage biotechs.