A recent Phase I/II clinical study led by UMass Chan Medical School has shown encouraging results for a gene therapy targeting GM2 gangliosidosis, a group of rare and fatal neurodegenerative disorders that includes Tay-Sachs and Sandhoff diseases. These conditions, as reported by World Pharma News, caused by genetic mutations that prevent proper breakdown of cellular molecules in the nervous system, lead to progressive nerve cell damage, severe developmental decline, and early childhood death. To date, there is no effective treatment.
In this pioneering trial, nine patients received a dual-vector gene therapy designed to deliver functional copies of the missing HEXA gene directly into the brain and spinal cord via harmless viral vectors. The therapy aimed to teach brain cells to produce the crucial HexA enzyme, which is otherwise deficient in these patients. The approach was validated by increased enzyme activity in all participants, with levels more than double the lower normal limit.
Lead investigator Dr. Heather Gray-Edwards reported that while therapeutic levels were not fully reached, the gene therapy vectors worked as intended and thalamic injections proved safe. Clinical improvements followed: participants maintained the ability to eat by mouth for extended periods—a key quality of life milestone—compared to historical controls who typically require intravenous feeding by 13–18 months of age. Notably, the two highest-dose patients remained on oral feeds through the study’s end (20 and 27 months). Additionally, seizures were less severe, less frequent, and more easily controlled with medication.
Importantly, the dual-vector approach was well tolerated, with minimal adverse reactions. The study’s biochemical and clinical impact was independently assessed by Massachusetts General Hospital, supporting the findings published in Nature Medicine. These results lay the groundwork for further development, giving families and clinicians hope for a transformative therapy for these devastating diseases.
Dr. Gray-Edwards and co-investigator Dr. Miguel Sena-Esteves plan to further improve the therapy by combining both gene vectors into a single vector. This would allow a greater dose of therapeutic DNA to be delivered without increasing the volume, potentially boosting effectiveness and enabling treatment at an even earlier stage—critical for preventing irreversible neuron loss.
The study was supported by patient advocacy groups and research foundations, underscoring the collaborative effort driving rare disease research forward. For now, these early results represent an essential step toward a long-sought treatment for Tay-Sachs, Sandhoff, and related GM2 gangliosidosis disorders, offering renewed hope to families affected by these relentless conditions.
