{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T02:16:53Z","timestamp":1785377813587,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T00:00:00Z","timestamp":1668211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015211","name":"Department of Education, Skills and Employment, Australian Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015211","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["10915693"],"award-info":[{"award-number":["10915693"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acquisition of drug\u2010sensitivity profiles is challenging in rare epilepsies. Anecdotal evidence suggests that antiseizure medications that block sodium channels as their primary mechanism of action exacerbate seizures in <jats:italic>HCN1<\/jats:italic> developmental and epileptic encephalopathies (DEEs), whereas sodium valproate is effective for some patients. The Hcn1 M294L heterozygous knock\u2010in (Hcn1<jats:sup>M294L<\/jats:sup>) mouse carries the homologue of the recurrent gain\u2010of\u2010function HCN1 M305L pathogenic variant and recapitulates the seizure and some behavioral phenotypes observed in patients. We used this mouse model to study drug efficacy in <jats:italic>HCN1<\/jats:italic> DEE. Hcn1<jats:sup>M294L<\/jats:sup> mice display epileptiform spiking on electrocorticography (ECoG), which we used as a quantifiable measure of drug effect. Phenytoin, lamotrigine, and retigabine significantly increased ECoG spike frequency, with lamotrigine and retigabine triggering seizures in a subset of the mice tested. In addition, there was a strong trend for carbamazepine to increase spiking. In contrast, levetiracetam, diazepam, sodium valproate, and ethosuximide all significantly reduced ECoG spike frequency. Drugs that reduced spiking did not cause any consistent ECoG spectral changes, whereas drugs that increased spiking all increased power in the slower delta and\/or theta bands. These data provide a framework on which to build our understanding of gain\u2010of\u2010function <jats:italic>HCN1<\/jats:italic> DEE pharmacosensitivity in the clinical setting.<\/jats:p>","DOI":"10.1111\/epi.17447","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T11:17:30Z","timestamp":1666869450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Efficacy of antiseizure medication in a mouse model of <i>HCN1<\/i> developmental and epileptic encephalopathy"],"prefix":"10.1111","volume":"64","author":[{"given":"Lauren E.","family":"Bleakley","sequence":"first","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaseley E.","family":"McKenzie","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1457-8028","authenticated-orcid":false,"given":"Christopher A.","family":"Reid","sequence":"additional","affiliation":[{"name":"Florey Institute of Neuroscience and Mental Health University of Melbourne  Parkville Victoria Australia"},{"name":"Epilepsy Research Centre, Department of Medicine, University of Melbourne Austin Health  Heidelberg Victoria 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