May 05, 2026 —
The National Institute of Neurological Disorders and Stroke has awarded Toloo Taghian, PhD, assistant professor of genetic & cellular medicine and radiology at UMass Chan Medical School, a five-year, $3.2 million grant to support the development of a gene therapy for UBA5 disorder, a rare and life-threatening neurological disease that typically begins in infancy.
UBA5 disorder, also known as developmental and epileptic encephalopathy 44 (DEE44), is caused by mutations in the UBA5 gene, which encodes a protein essential for UFMylation—a cellular process involved in maintaining protein balance and protecting cells from stress. When UBA5 activity is disrupted, protein function and cellular homeostasis are impaired, leading to severe neurological consequences. The disease is extremely rare, with roughly 40 diagnosed cases worldwide, and there is currently no known cure. Available care is limited to symptom management.
One of the major challenges in developing therapies for ultra-rare diseases such as UBA5 disorder is the limited understanding of disease biology. Because so few patients have been identified, the cellular pathways, molecular mechanisms, biomarkers, and clinical progression of the disease remain poorly defined. The new grant will support research into the initiation and progression of UBA5 disorder, biomarker discovery, and the development of clinically relevant metrics that could help monitor disease progression and evaluate future therapeutic efficacy.
A central focus of the program is the development of an AAV9-based gene therapy designed to deliver a normal copy of the UBA5 gene to affected cells. With support from the Raiden Science Foundation, a nonprofit founded by Tommy and Linda Pham, whose son Raiden has UBA5 disorder, Dr. Taghian’s team has already developed a UBA5-expressing AAV9 vector that may restore normal cellular function by correcting the underlying genetic deficiency.
The program is also moving toward clinical translation. In late 2025, UMass Chan submitted a pre-investigational new drug package to the FDA for a potential gene therapy clinical trial in UBA5 disorder. The new NINDS funding is expected to strengthen the translational foundation for this program by supporting mechanistic research, biomarker development, and trial-enabling strategies.
This grant highlights the growing importance of academic and foundation-driven innovation in rare disease gene therapy. For ultra-rare neurological disorders such as UBA5 disorder, where commercial incentives may be limited and patient populations are extremely small, targeted funding and patient-family advocacy can play a critical role in moving promising AAV gene therapy programs from early discovery toward the clinic.
