ArticleAnnals of neurology2014
KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine.
Article in Annals of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 3 of them syntheses that pooled it.
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Who cites it
114 citing papers in PubMed, 3 syntheses or guidelines pooled it, 294 citations in OpenAlex.
- Efficacy of anti-seizure medications and alternative therapies (ketogenic diet, CBD, and quinidine) in KCNT1-related epilepsy: A systematic review.Epilepsia open · 2024Pooled it
- New use for an old drug: quinidine in KCNT1-related epilepsy therapy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Pooled it
- Intellectual Disability and Potassium Channelopathies: A Systematic Review.Frontiers in genetics · 2020Pooled it
- RNA targeting therapy for a prenatally enriched potassium channel associated with severe childhood epilepsy and premature death.Nature communications · 2026Article
- Antisense oligonucleotide-mediated knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy.Nature medicine · 2026Article
- Unraveling the mechanisms of slack channel mutations in epileptic disorders.Acta epileptologica · 2026Review
- Identification of New KCNT1-Epilepsy Drugs by In Silico, Cell, and Drosophila Modeling.Annals of neurology · 2025Article
- Diverse species of animal models in epilepsy research: Progress and perspectives.Zoological research · 2025Review
- Fluoxetine Treatment in Epilepsy of Infancy with Migrating Focal Seizures Due to KCNT1 Variants: An Open Label Study.Annals of neurology · 2025Article
- KCNT1 gene variant-associated epilepsy: genetic insights, functional mechanisms, and emerging therapies.Journal of neurology · 2025Review
- Precision therapies for genetic epilepsies in 2025: Promises and pitfalls.Epilepsia open · 2025Article
- Electrophysiological characterization of human KCNT1 channel modulators and the therapeutic potential of hydroquinine and tipepidine in KCNT1 mutation-associated epilepsy mouse model.Acta pharmacologica Sinica · 2025Article
- International Precision Child Health Partnership (IPCHiP): an initiative to accelerate discovery and improve outcomes in rare pediatric disease.NPJ genomic medicine · 2025Review
- Structure-Activity Relationship Studies in a Series of 2-Aryloxy-Molecules (Basel, Switzerland) · 2024Article
- Voltage-Gated Ion Channel Compensatory Effect in DEE: Implications for Future Therapies.Cells · 2024Review
- Heterozygous expression of aeLife · 2024Article
- WONOEP appraisal: Modeling early onset epilepsies.Epilepsia · 2024Review
- New epilepsy therapies in development.Nature reviews. Drug discovery · 2024Review
- Heterozygous expression of abioRxiv : the preprint server for biology · 2024Article
- KCNT1 Channel Blockers: A Medicinal Chemistry Perspective.Molecules (Basel, Switzerland) · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
objectiveMutations in KCNT1 have been implicated in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of infancy with migrating focal seizures (EIMFS). More recently, a whole exome sequencing study of epileptic encephalopathies identified an additional de novo mutation in 1 proband with EIMFS. We aim to investigate the electrophysiological and pharmacological characteristics of hKCNT1 mutations and examine developmental expression levels.
methodsHere we use a Xenopus laevis oocyte-based automated 2-electrode voltage clamp assay. The effects of quinidine (100 and 300 μM) are also tested. Using quantitative reverse transcriptase polymerase chain reaction, the relative levels of mouse brain mKcnt1 mRNA expression are determined.
resultsWe demonstrate that KCNT1 mutations implicated in epilepsy cause a marked increase in function. Importantly, there is a significant group difference in gain of function between mutations associated with ADNFLE and EIMFS. Finally, exposure to quinidine significantly reduces this gain of function for all mutations studied.
interpretationThese results establish direction for a targeted therapy and potentially exemplify a translational paradigm for in vitro studies informing novel therapies in a neuropsychiatric disease.
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