AUTHOR=Hill Sophie F. , Jafar-Nejad Paymaan , Rigo Frank , Meisler Miriam H. 

TITLE=Reduction of Kcnt1 is therapeutic in mouse models of SCN1A and SCN8A epilepsy

JOURNAL=Frontiers in Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1282201

DOI=10.3389/fnins.2023.1282201

ISSN=1662-453X

ABSTRACT=<p>Developmental and epileptic encephalopathies (DEEs) are severe seizure disorders with inadequate treatment options. Gain- or loss-of-function mutations of neuronal ion channel genes, including potassium channels and voltage-gated sodium channels, are common causes of DEE. We previously demonstrated that reduced expression of the sodium channel gene <italic>Scn8a</italic> is therapeutic in mouse models of sodium and potassium channel mutations. In the current study, we tested whether reducing expression of the potassium channel gene <italic>Kcnt1</italic> would be therapeutic in mice with mutation of the sodium channel genes <italic>Scn1a</italic> or <italic>Scn8a</italic>. A <italic>Kcnt1</italic> antisense oligonucleotide (ASO) prolonged survival of both <italic>Scn1a</italic> and <italic>Scn8a</italic> mutant mice, suggesting a modulatory effect for KCNT1 on the balance between excitation and inhibition. The cation channel blocker quinidine was not effective in prolonging survival of the <italic>Scn8a</italic> mutant. Our results implicate <italic>KCNT1</italic> as a therapeutic target for treatment of <italic>SCN1A</italic> and <italic>SCN8A</italic> epilepsy.</p>