KCNT1 mRNA

Class

antisense oligonucleotide (ASO) designed by Servier to degrade KCNT1 messenger RNA, a gene-targeted (not small-molecule) approach

Pathway

degrades KCNT1 mRNA to reduce expression of the mutated, overactive KCNT1 channel underlying KCNT1-related developmental and epileptic encephalopathy (KCNT1-DEE)

KCNT1 encodes a potassium channel activated by rising sodium levels inside neurons. After a nerve cell fires, this channel opens and lets potassium exit, helping reset the cell so it does not fire again too quickly. In a group of severe, early-onset epilepsies known collectively as KCNT1-related developmental and epileptic encephalopathy, inherited mutations make the channel overactive, a gain-of-function change that disrupts normal neuronal firing patterns, particularly in inhibitory circuits, and produces frequent, treatment-resistant seizures along with developmental delay. Because the disease arises from too much channel activity rather than too little, one therapeutic strategy is to reduce how much channel protein neurons produce in the first place, rather than trying to block an already-formed channel with a small molecule. Antisense oligonucleotides achieve this by binding directly to the KCNT1 messenger RNA transcript and flagging it for enzymatic breakdown before it can be translated into protein. This gene-targeted approach addresses the underlying cause of disease rather than only its downstream electrical consequences, and reflects a broader strategy under exploration for other single-gene channelopathies where a dominant mutation drives excessive channel or receptor activity.