{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T14:10:21Z","timestamp":1777039821880,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T00:00:00Z","timestamp":1691280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P50HD105351"],"award-info":[{"award-number":["P50HD105351"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder caused by autosomal\u2010dominant pathogenic variants in either the <jats:italic>TSC1<\/jats:italic> or <jats:italic>TSC2<\/jats:italic> gene, and it is characterized by hamartomas in multiple organs, such as skin, kidney, lung, and brain. These changes can result in epilepsy, learning disabilities, and behavioral complications, among others. The mechanistic link between TSC and the mechanistic target of the rapamycin (mTOR) pathway is well established, thus mTOR inhibitors can potentially be used to treat the clinical manifestations of the disorder, including epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we tested the efficacy of a novel mTOR catalytic inhibitor (here named Tool Compound 1 or TC1) previously reported to be more brain\u2010penetrant compared with other mTOR inhibitors. Using a well\u2010characterized hypomorphic <jats:italic>Tsc2<\/jats:italic> mouse model, which displays a translationally relevant seizure phenotype, we tested the efficacy of TC1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results show that chronic treatment with this novel mTOR catalytic inhibitor (TC1), which affects both the mTORC1 and mTORC2 signaling complexes, reduces seizure burden, and extends the survival of <jats:italic>Tsc2<\/jats:italic> hypomorphic mice, restoring species typical weight gain over development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Novel mTOR catalytic inhibitor TC1 exhibits a promising therapeutic option in the treatment of TSC.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51868","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T04:40:24Z","timestamp":1691383224000},"page":"1790-1801","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Seizure reduction in <scp>TSC2<\/scp>\u2010mutant mouse model by an <scp>mTOR<\/scp> catalytic inhibitor"],"prefix":"10.1002","volume":"10","author":[{"given":"Sameer C.","family":"Dhamne","sequence":"first","affiliation":[{"name":"F.M. 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