Catalyst Award

Preclinical IND Enabling Studies of TrkB Peptide

James O. McNamara, MD
Duke University

Temporal Lobe Epilepsy (TLE) is a common form of epilepsy with an estimated 35% of patients having recurrent seizures despite treatment with anticonvulsants. Dr. McNamara and other researchers previously discovered that proteins in the brain called BDNF and TrkB play an important role in the development of TLE in animal models. Dr. McNamara’s team further found that BDNF/TrkB can cause epileptogenesis through activation of another protein called PLCgamma1. This led to their discovery of a novel peptide, pY816, which blocks the activation of PLCgamma1 and prevents epileptogenesis in animal models.

The goal of this translational research project is to conduct key studies to advance pY816 to human clinical trials for TLE. Specifically, the team will develop an assay to reliably detect pY816 in the blood of treated animals and conduct studies to determine the best dose which causes minimal toxicity in the animals.

In a previous grant funded by CURE Epilepsy, Dr. McNamara studied the role of TrkB in post-traumatic epilepsy in animal models. For his Catalyst Award funded by the Robert Withrow Wier Grant, his current set of studies will focus on advancing the development of pY816 as a novel therapy for drug-resistant TLE.