title: The promise of an interneuron-based cell therapy for epilepsy.
abstract: Of the nearly 3 million Americans diagnosed with epilepsy, approximately 30% are unresponsive to current medications. Recent data has shown that early postnatal transplantation of interneuronal precursor cells increases GABAergic inhibition in the host brain and dramatically suppresses seizure activity in epileptic mice. In this review, we will highlight findings from seizure-prone mice and humans that demonstrate the link between dysfunctional GABAergic inhibition and hyperexcitability. In particular, we will focus on rodent models of temporal lobe epilepsy, the most common and difficult to treat form of the disease, and interneuronopathies, an emerging classification. A wealth of literature showing a causal link between reduced GABA-mediated inhibition and seizures has directed our efforts to recover the loss of inhibition via transplantation of interneuronal precursors. Numerous related studies have explored the anticonvulsant potential of cell grafts derived from a variety of brain regions, yet the mechanism underlying the effect of such heterogeneous cell transplants is unknown. In discussing our recent findings and placing them in context with what is known about epilepsy, and how related transplant approaches have progressed, we hope to initiate a frank discussion of the best path toward the translation of this approach to patients with intractable forms of epilepsy.
authors.affiliation: Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, San Francisco, California, USA. joysebe@gmail.com
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Sebe
authors.forename: Scott C
authors.initials: SC
authors.lastname: Baraban
mesh_terms: D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods* / Q000639:trends; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends