Toward an Innovative Treatment for Pyridoxine-Dependent Epilepsy

Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder causing seizures due to errors in a specific gene, which damage a protein called “antiquitin.” PDE occurs in 1 in 100,000 to 700,000 individuals worldwide, with at least 100 cases reported. Current treatment, relying on dietary supplements of pyridoxine, does not offer a complete solution. Paula Waters, together with co-investigators Marion Coulter-Mackie and Sylvia Stockler, is working toward an innovative new treatment for PDE. Their aim is to decrease the effects of genetic errors on the antiquitin protein by first doing studies to understand how genetic errors affect the structure and function of the antiquitin protein. Second, they will determine whether these consequences can be reversed by identifying so-called “molecular chaperones,” which can rescue the protein. If successful, this method may open the door to treating other types of rare genetic epilepsies.