Efficacy of antiseizure medication in a mouse model of HCN1 developmental and epileptic encephalopathy.

ABSTRACT: Acquisition of drug-sensitivity 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 HCN1 developmental and epileptic encephalopathies (DEEs), whereas sodium valproate is effective for some patients. The Hcn1 M294L heterozygous knock-in (Hcn1^M294L ) mouse carries the homologue of the recurrent gain-of-function 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 HCN1 DEE. Hcn1^M294L mice display epileptiform spiking on electrocorticography (ECoG), which we used as a quantifiable measure of drug effect. Phenytoin, lamotrigine, a

SUBMITTER: Bleakley LE 

PROVIDER: S-EPMC10953365 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature