UBA5-Related Epilepsy: From Cellular Models to Novel Therapies
St. Jude Children’s Research Hospital
2024
Heather Mefford, MD, PhD
Genetic changes in a gene called ubiquitin like modifier activating enzyme 5 (UBA5) cause a rare disorder with developmental delays, abnormal muscle tone, and hard-to-treat seizures. People with this disorder have changes in both copies of the UBA5 gene (one from each parent), leading to decreased activity of the UBA5 protein. To better understand how these changes affect brain development, Dr. Mefford’s team will study 3D disease-in-a-dish models (called brain organoids) made from patient cells. They will then test at least two methods to increase the amount of UBA5 protein as a potential treatment. These methods for modeling the disease using patient cells and approaches to gene-targeted treatment could also apply to other genes that cause epilepsy, where increasing gene expression might be a possible treatment.
