Photo: Faith Ninivaggi
The National Institute of Neurological Disorders and Stroke has awarded Toloo Taghian, PhD, assistant professor of genetic & cellular medicine and radiology, a five-year, $3.2 million grant to develop a gene therapy for UBA5 disorder, a rare genetic disease that typically manifests in infancy.
“One of the biggest challenges working on each of the rare diseases for the first time is that the cellular pathways and molecular mechanisms of the disease are hidden in a black box because there is limited research and so few patients from which to learn,” said Dr. Taghian. “It’s not easy to develop an effective treatment when you don’t understand the biology driving the disease. This grant allows us to investigate the initiation and progression of the UBA5 disorder, discover biomarkers and develop the next generation of transformative gene therapies for UBA5 disease.”
UBA5 disorder (also known as developmental and epileptic encephalopathy 44 or DEE44) is a life-threatening, progressive neurological disease that typically manifests in infancy. The UBA5 gene encodes a protein crucial for UFMylation, a fundamental process in cellular homeostasis that maintains protein balance and protects cells from stress. UBA5 disease occurs when mutations in the UBA5 gene affect the normal UBA5 activity, leading to protein malfunction and impaired cell function, with neurological impacts. There is no known cure for UBA5 disorder. In the roughly 40 cases diagnosed worldwide, managing symptoms is the only available treatment option.
“Patients with UBA5 disorder often succumb to the disease in childhood,” said Taghian. “One goal of this grant is to develop clinically relevant metrics to enable monitoring the disease progression in patients and determine the efficacy of future clinical trials for UBA5 disorder, which streamlines translation of UBA5 gene therapy from bench to clinic.”
Gene therapy treatments seek to modify, augment, silence or replace disease-causing genes, often using a normal copy of the gene. Delivered through various nonviral or viral systems, such as the adeno-associated virus (AAV), DNA sequences can be delivered into targeted cells to treat genetic diseases.
With funding from the Raiden Science Foundation, a nonprofit started by Tommy and Linda Pham, whose 6-year-old son Raiden has UBA5 disorder, a team of scientists at UMass Chan Medical School led by Taghian has developed a UBA5-expressing AAV9 vector that could potentially deliver a normal copy of the UBA5 gene to patients, thereby restoring normal cell function. In late 2025, UMass Chan submitted a pre-investigational new drug package to the Food and Drug Administration for a gene therapy clinical trial in UBA5 disorder.
Taghian joined UMass Chan in 2016 as a postdoctoral associate in the lab of Alexi Bogdanov Jr. PhD, professor of radiology. In 2018 she joined the lab of Heather Gray-Edwards, DVM, PhD, assistant professor of genetic & cellular medicine, where she worked on a gene therapy treatment for Tay-Sachs disease, another rare genetic neurological disorder. She became an instructor in radiology and a member of the Horae Gene Therapy Center at UMass Chan in 2021, and was promoted to assistant professor in 2025.
From 2019 to 2020, Taghian held a postdoctoral fellowship from the Horae Gene Therapy Center. She received the Excellence in Research Award from the American Society of Gene & Cell Therapy at the ASGCT 24th Annual Meeting in 2021 and received the Uplifting Athletes Young Investigator Draft Award in 2024 for her research in rare diseases.
