Anup Kumar Srivastava, PhD, MSc
Multi-Focal Delivery of Nav1.1-Expressing GABAergic Progenitor Cells for Treatment of Dravet Syndrome
Abstract
Dravet syndrome (DS) is pediatric epilepsy characterized by recurrent seizures, developmental delays, cognitive impairment, and sudden unexpected death due to epilepsy (SUDEP). Mutations in the SCN1A gene encoding the sodium channel (Nav1.1) in GABAergic neurons lead to imbalanced excitatory and inhibitory (E/I) transmission. We hypothesized that GABAergic progenitor cell (GPC) therapy could be promising in restoring the E/I balance, but the obstacles of administration routes, cell retention, and functional brain integration must be overcome. In this study, we will test the efficacy of Nav1.1-overexpressing GPCs delivered in the brains of DS mice using a 3D-printed, hydrogel-inspired, porous, micron-sized cell delivery vehicle (Biocage) for direct, multi-focal delivery. This locoregional delivery will improve the functional integration of differentiated GABAergic neurons in the mouse model of DS, rebalance E/I neurotransmission, and prevent DS-associated SUDEP.
