Federal Grant Award Summary

The University of Massachusetts Medical School received a $659,245 Project Grant award, effective March 1, 2026 through February 28, 2031, from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853). This award supports the development of a gene therapy treatment for UBA5 (Ubiquitin Like Modifier Activating Enzyme 5) deficiency, an ultra-rare autosomal recessive neurological disorder characterized by infantile spasms, developmental delay, seizures, and progressive neurological decline with high childhood mortality rates. Currently, clinical management is limited to symptomatic treatment with anti-seizure medications and physical therapies, with no disease-modifying intervention available.

The research project leverages the institution's newly developed mouse model of UBA5 deficiency that recapitulates the human disease phenotype and access to postmortem brain tissue from UBA5 patients to advance gene therapy development. The research team has identified an adeno-associated virus (AAV) vector candidate, AAV9-JET-UBA5, that demonstrated restoration of motor and cognitive function in the disease model following neonatal intracerebroventricular treatment. The funded project will conduct preclinical efficacy and safety studies to advance this therapeutic candidate toward potential clinical application for this currently untreatable pediatric neurological disorder.