Approaches for the discovery of drugs that target K Na 1.1 channels in KCNT1-associated epilepsy

Expert Opin Drug Discov. 2022 Dec;17(12):1313-1328. doi: 10.1080/17460441.2023.2150164. Epub 2022 Nov 24.


Introduction: There are approximately 70 million people with epilepsy and about 30% of patients are not satisfactorily treated. A link between gene mutations and epilepsy is well documented. A number of pathological variants of KCNT1 gene (encoding the weakly voltage-dependent sodium-activated potassium channel - KNa 1.1) mutations has been found. For instance, epilepsy of infancy with migrating focal seizures, autosomal sleep-related hypermotor epilepsy or Ohtahara syndrome have been associated with KCNT1 gene mutations.

Areas covered: Several methods for studies on KNa 1.1 channels have been reviewed - patch clamp analysis, Förster resonance energy transfer spectroscopy and whole-exome sequencing. The authors also review available drugs for the management of KCNT1 epilepsies.

Expert opinion: The current methods enable deeper insights into electrophysiology of KNa 1.1 channels or its functioning in different activation states. It is also possible to identify a given KCNT1 mutation. Quinidine and cannabidiol show variable efficacy as add-on to baseline antiepileptic drugs so more effective treatments are required. A combined approach with the methods shown above, in silico methods and the animal model of KCNT1 epilepsies seems likely to create personalized treatment of patients with KCNT1 gene mutations.

Keywords: Förster resonance energy transfer spectroscopy; KCNT1 epilepsy; cannabidiol; patch clamp; quinidine; seizures; whole exome sequencing.

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Epilepsy* / drug therapy
  • Epilepsy* / genetics
  • Mutation
  • Potassium Channels, Sodium-Activated / genetics
  • Seizures / drug therapy


  • Potassium Channels, Sodium-Activated
  • Anticonvulsants