An Interneuron-based Cell Therapy for Epilepsy

Project Summary/Abstract
Cell transplantation, using GABAergic interneurons that integrate in host brain circuits, and function similar to
endogenous inhibitory neurons could offer a novel therapeutic alternative for intractable epilepsies. Our work,
over the past two decades, demonstrated that GABAergic progenitor cells derived from murine embryonic medial
ganglionic eminence (MGE) integrate into host circuits (following transplantation in neonatal or adult mice),
where they make functional inhibitory synapses, efficiently suppress epileptic seizure activity, and correct
behavioral comorbidities associated with epilepsy. To establish an alternative source of MGE progenitor cells
that would facilitate translation of this disease-modifying transplantation strategy to larger species, we recently
established protocols using porcine embryonic MGE progenitor cells. Building on these findings, two specific
aims are proposed: (i) to optimize intra-hippocampal xenotransplantation of porcine embryonic MGE progenitor
cells and (ii) to evaluate the range of therapeutic benefits possible with porcine embryonic MGE progenitor cells.
Techniques will involve cutting-edge electrophysiology, optogenetic and calcium imaging methods (in vitro and
in vivo) to study functional integration of MGE-derived interneurons. Video-EEG monitoring, rodent epilepsy
models, sophisticated behavioral assays, and confocal microscopy techniques will also be applied. Our results
promise to provide new information about porcine MGE progenitors and direct demonstration(s) of the potential
for xenotransplantation as a treatment for intractable epilepsies.

Grant Number: 5R01NS071785-17
NIH Institute/Center: NIH
Principal Investigator: Scott Baraban