{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:46:22Z","timestamp":1776750382747,"version":"3.51.2"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Patients with drug\u2010resistant epilepsy, including Dravet syndrome, are frequently prescribed multiple antiseizure medications. Nevertheless, people with Dravet syndrome often have inadequate seizure control, and there is an ongoing unmet clinical need to identify novel therapeutics. As a proof\u2010of\u2010principle study to further validate and characterize the\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>A1783V\/WT<\/jats:italic>\n                      <\/jats:sup>\n                      mouse model and identify a drug\u2010testing paradigm with face, construct, and predictive validity, we assessed the efficacy of subchronic administration of stiripentol add\u2010on to clobazam and valproic acid at clinically relevant doses using the\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>A1783V\/WT<\/jats:italic>\n                      <\/jats:sup>\n                      mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Following a 14\u2010day treatment, we evaluated the efficacy of stiripentol add\u2010on to clobazam and valproic acid using hyperthermia\u2010induced (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096) and video\u2010electroencephalography (EEG) monitoring of spontaneous seizure tests (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200913). Valproic acid was delivered via osmotic minipump, whereas stiripentol and clobazam were administered via food pellets delivered through automatic feeders. Bioanalytical assays were performed to evaluate drug concentrations in plasma and brain using liquid chromatography\u2013tandem mass spectrometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Stiripentol, clobazam,\n                      <jats:italic>N<\/jats:italic>\n                      \u2010desmethylclobazam, and valproic acid all yielded plasma concentrations within the therapeutic plasma concentration range for humans. Stiripentol added to clobazam and valproic acid significantly elevated the seizing temperatures in the hyperthermia\u2010induced seizure assay (**\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0018; Log\u2010rank test). Clobazam, valproic acid, and stiripentol co\u2010administration significantly reduced spontaneous seizure frequency compared to clobazam and valproic acid combined (***\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003, Mann\u2013Whitney test).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      This research lays the groundwork for exploring effective add\u2010on compounds to clobazam and valproic acid in treating Dravet syndrome. The study further highlights the utility of the\n                      <jats:italic>Scn1a<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>A1783V\/WT<\/jats:italic>\n                      <\/jats:sup>\n                      mice in discovering therapies for Dravet syndrome\u2013associated pharmacoresistant seizures.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18516","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T10:39:18Z","timestamp":1751279958000},"page":"4023-4034","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development of a preclinical testing platform for clinically relevant therapy for Dravet syndrome"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7026-9329","authenticated-orcid":false,"given":"Jeffrey 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