University of Pennsylvania Department of Physiology Retreat

STXBP1 and SYNGAP1 encode for pre-and post-synaptic proteins that are required for neurotransmission and synaptic plasticity, respectively. Variants in these genes lead to rare, complex and debilitating neurological disorders. Currently there are no treatments capable of altering the course of these diseases, and little is known about the natural progression of these disorders nor their presentation in adults. Our group in the recently formed Center for Epilepsy and Neurodevelopmental Disorders (ENDD) aims to both develop novel gene-based therapies to treat these disorders and to clinically define their presentation and trajectory to enable future clinical trials. Here I will provide both an overview of the challenges and strategies taken to achieve these translational and clinical research goals, as well as a more detailed examination of one of our lead therapeutic strategies – the use of antisense-oligonucleotides (ASOs) to target and manipulate mRNA processing in order to restore expression of STXBP1 and SYNGAP1.