학술논문
Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy.
Document Type
article
Author
Bershteyn, Marina; Bröer, Sonja; Parekh, Mansi; Maury, Yves; Havlicek, Steven; Kriks, Sonja; Fuentealba, Luis; Lee, Seonok; Zhou, Robin; Subramanyam, Geetha; Sezan, Meliz; Sevilla, Eric; Blankenberger, Whitney; Spatazza, Julien; Zhou, Li; Nethercott, Hubert; Traver, David; Hampel, Philip; Kim, Hannah; Watson, Michael; Salter, Naomi; Nesterova, Anastasia; Au, Wai; Banik, Gautam; Bulfone, Alessandro; Priest, Catherine; Nicholas, Cory; Kriegstein, Arnold; Rubenstein, John; Alvarez-Buylla, Arturo
Source
Cell Stem Cell. 30(10)
Subject
Language
Abstract
Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy. One-third of patients have drug-refractory seizures and are left with suboptimal therapeutic options such as brain tissue-destructive surgery. Here, we report the development and characterization of a cell therapy alternative for drug-resistant MTLE, which is derived from a human embryonic stem cell line and comprises cryopreserved, post-mitotic, medial ganglionic eminence (MGE) pallial-type GABAergic interneurons. Single-dose intrahippocampal delivery of the interneurons in a mouse model of chronic MTLE resulted in consistent mesiotemporal seizure suppression, with most animals becoming seizure-free and surviving longer. The grafted interneurons dispersed locally, functionally integrated, persisted long term, and significantly reduced dentate granule cell dispersion, a pathological hallmark of MTLE. These disease-modifying effects were dose-dependent, with a broad therapeutic range. No adverse effects were observed. These findings support an ongoing phase 1/2 clinical trial (NCT05135091) for drug-resistant MTLE.