Chemogenetics with PSAM⁴-GlyR decreases excitability and epileptiform activity in epileptic hippocampus.

ABSTRACT: Despite the availability of new drugs on the clinics in recent years, drug-resistant epilepsy remains an unresolved challenge for healthcare, and one-third of epilepsy patients remain refractory to anti-seizure medications. Gene therapy in experimental models has emerged as effective treatment targeting specific neuronal populations in the epileptogenic focus. When combined with an external chemical activator using chemogenetics, it also becomes an "on-demand" treatment. Here, we evaluate a targeted and specific chemogenetic therapy, the PSAM/PSEM system, which holds promise as a potential candidate for clinical application in treating drug-resistant epilepsy. We show that the inert ligand uPSEM⁸¹⁷, which selectively activates the chloride-permeable channel PSAM⁴-GlyR

SUBMITTER: Gonzalez-Ramos A 

PROVIDER: S-EPMC11946892 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature