Cell stem cell · 2023
Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Bershteyn Marina, Bröer Sonja, 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
Аннотация
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.