Catalyst Award

Safety and Biodistribution of a Novel Enzyme-Antibody Fusion in a Canine Model

James Pauly, PhD
University of Kentucky

Lafora disease (LD) is a devastating and fatal childhood epilepsy that currently has no treatments. A hallmark of LD is aberrant sugar-like aggregates that form in brain cells. In mouse models of LD, scientists have shown that removal of these sugar aggregates may be a potential therapy for this devastating disease.  In collaboration with Enable Therapeutics, Drs. Pauly, Gerhardt, and Gentry developed a drug called VAL-1221 that can penetrate into cells and degrade the aberrant sugar aggregates. In a series of published papers, they have shown that this approach completely clears mouse brains of the aggregates.  Due to the blood-brain barrier which prevents substances from getting into the brain, VAL-1221 must be injected directly into a cavity in the brain called the cerebroventricular space. Having obtained promising initial results in mouse models, this project will now test the safety and brain distribution of this novel therapy in a canine model. Results from this research will help the team acquire the necessary data to move this therapy closer to clinical application.