{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:04:00Z","timestamp":1792728240382,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Dravet syndrome (DS) is a rare but catastrophic genetic epilepsy, with 80% of patients carrying a mutation in the\n                      <jats:italic>SCN1A<\/jats:italic>\n                      gene. Currently, no antiseizure drug (ASD) exists that adequately controls seizures. In the clinic, individuals with DS often present first with a febrile seizure and, subsequently, generalized tonic\u2010clonic seizures that can continue throughout life. To facilitate the development of ASDs for DS, the contract site of the National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP) has evaluated a mouse model of DS using the conditional knock\u2010in\n                      <jats:italic>\n                        Scn1a\n                        <jats:sup>A1783V\/WT<\/jats:sup>\n                      <\/jats:italic>\n                      mouse.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Survival rates and temperature thresholds for\n                      <jats:italic>\n                        Scn1a\n                        <jats:sup>A1783V\/WT<\/jats:sup>\n                      <\/jats:italic>\n                      were determined. Prototype ASDs were administered via intraperitoneal injections at the time\u2010to\u2010peak effect, which was previously determined, prior to the induction of hyperthermia\u2010induced seizures. ASDs were considered effective if they significantly increased the temperature at which\n                      <jats:italic>\n                        Scn1a\n                        <jats:sup>A1783V\/WT<\/jats:sup>\n                      <\/jats:italic>\n                      mice had seizures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Approximately 50% of\n                      <jats:italic>\n                        Scn1a\n                        <jats:sup>A1783V\/WT<\/jats:sup>\n                      <\/jats:italic>\n                      survive to adulthood and all have hyperthermia\u2010induced seizures. The results suggest that hyperthermia\u2010induced seizures in this model of DS are highly refractory to a battery of ASDs. Exceptions were clobazam, tiagabine, levetiracetam, and the combination of clobazam and valproic acid with add\u2010on stiripentol, which elevated seizure thresholds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Overall, the data demonstrate that the proposed model for DS is suitable for screening novel compounds for the ability to block hyperthermia\u2010induced seizures and that heterozygous mice can be evaluated repeatedly over the course of several weeks, allowing for higher throughput screening.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.16925","type":"journal-article","created":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T02:34:58Z","timestamp":1621305298000},"page":"1665-1676","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Development of an antiseizure drug screening platform for Dravet syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-7086","authenticated-orcid":false,"given":"Chelsea D.","family":"Pernici","sequence":"first","affiliation":[{"name":"Epilepsy Therapy Screening Program (ETSP) Contract Site University of Utah Salt Lake City UT USA"},{"name":"Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Mensah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misty D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Epilepsy Therapy Screening Program (ETSP) Contract Site University of Utah Salt Lake City UT USA"},{"name":"Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"West","sequence":"additional","affiliation":[{"name":"Epilepsy Therapy Screening Program (ETSP) Contract Site University of Utah Salt Lake City UT USA"},{"name":"Department of Pharmacology and Toxicology University of Utah Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1510-0405","authenticated-orcid":false,"given":"Cameron S.","family":"Metcalf","sequence":"additional","affiliation":[{"name":"Epilepsy Therapy Screening Program (ETSP) 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