Publikationsdatenbank

Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy (2023)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Bershteyn, Marina

Bröer, Sonja (WE 14)

Parekh, Mansi

Maury, Yves

Havlicek, Steven

Kriks, Sonja

Fuentealba, Luis

Lee, Seonok

Zhou, Robin

Subramanyam, Geetha

Sezan, Meliz

Sevilla, Eric Steven

Blankenberger, Whitney

Spatazza, Julien

Zhou, Li

Nethercott, Hubert

Traver, David

Hampel, Philip

Kim, Hannah

Watson, Michael

Salter, Naomi

Nesterova, Anastasia

Au, Wai

Kriegstein, Arnold

Alvarez-Buylla, Arturo

Rubenstein, John

Banik, Gautam

Bulfone, Alessandro

Priest, Catherine

Nicholas, Cory R.

Quelle

Cell stem cell

Bandzählung: 30

Heftzählung: 10

Seiten: 1331 – 1350.e11

ISSN: 1875-9777

Sprache

Englisch

Verweise

URL (Volltext): https://linkinghub.elsevier.com/retrieve/pii/S1934590923002965

DOI: 10.1016/j.stem.2023.08.013

Pubmed: 37802038

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

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.