Reduction of is therapeutic in mouse models of and epilepsy.

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 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 would be therapeutic in mice with mutation of the sodium channel genes or . A antisense oligonucleotide (ASO) prolonged survival of both and 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 mutant. Our results implicate as a therapeutic target for treatment of and epilepsy.