July 21, 2026 —
A UMass Chan Medical School research team has received authorization from the U.S. Food and Drug Administration to proceed with a Phase 1/2 clinical trial of a second-generation AAV gene therapy for GM2 gangliosidosis, a group of rare inherited neurodegenerative disorders that includes Tay-Sachs disease and Sandhoff disease.
The trial will be led by Heather Gray-Edwards, DVM, PhD, associate professor of genetic & cellular medicine, and Miguel Sena-Esteves, PhD, associate professor of genetic & cellular medicine. The program builds on more than a decade of research at UMass Chan focused on developing gene therapy approaches for GM2 gangliosidosis.
GM2 gangliosidosis disorders are caused by genetic mutations that impair the body’s ability to break down certain fatty substances. This leads to progressive accumulation of toxic materials and damage to the brain and nervous system. The diseases most often present in infancy, with symptoms including slow growth, developmental regression, poor muscle tone, seizures, and loss of motor function.
The infantile forms of GM2 gangliosidosis are universally fatal, with most affected children surviving only a few years. Other forms can present later in childhood, adolescence, or adulthood. There are currently no approved treatments for GM2 gangliosidosis.
The newly authorized trial will evaluate the safety and potential efficacy of a second-generation investigational AAV gene therapy. According to UMass Chan, the updated approach incorporates improvements intended to enhance delivery of the therapeutic genes to affected cells and achieve potential therapeutic benefit at lower doses than earlier strategies.
The program follows previous clinical research by the UMass Chan team that showed encouraging findings and supported continued development of a next-generation therapy. The new trial represents another step toward evaluating whether improved AAV delivery can address the root cause of Tay-Sachs and Sandhoff diseases.
The work also reflects UMass Chan’s broader commitment to developing genetic medicines for ultra-rare diseases that may have limited commercial interest but substantial unmet medical need. By advancing academic-led gene therapy programs, the institution aims to help bring investigational treatment options to children and families affected by severe inherited disorders.
If successful, the Phase 1/2 trial could provide important clinical evidence for second-generation AAV-based treatment of GM2 gangliosidosis and support continued development of gene therapies for rare pediatric neurodegenerative diseases.
