Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy.

Autor:	Bershteyn M; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Bröer S; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Parekh M; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Maury Y; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Havlicek S; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Kriks S; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Fuentealba L; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Lee S; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Zhou R; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Subramanyam G; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Sezan M; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Sevilla ES; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Blankenberger W; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Spatazza J; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Zhou L; Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA., Nethercott H; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Traver D; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Hampel P; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Kim H; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Watson M; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Salter N; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Nesterova A; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Au W; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Kriegstein A; Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA., Alvarez-Buylla A; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA., Rubenstein J; Department of Psychiatry, Weill Institute for Neurosciences, Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA., Banik G; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Bulfone A; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Priest C; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA., Nicholas CR; Neurona Therapeutics Inc., South San Francisco, CA 94080, USA. Electronic address: cory@neuronatx.com.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2023 Oct 05; Vol. 30 (10), pp. 1331-1350.e11.
DOI:	10.1016/j.stem.2023.08.013
Abstrakt:	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. Competing Interests: Declaration of interests All authors except for L.Z. are employees and/or shareholders of Neurona Therapeutics Inc. C.R.N., J.R., A.K., and A.A.-B. are founders of Neurona. J.R., A.K., and A.A.-B. are members of the scientific advisory board at Neurona. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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