ArticleJCI insight2022
Antisense oligonucleotide therapy for KCNT1 encephalopathy.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 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
- RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine.International journal of molecular sciences · 2026Review
- Engineering the Future of Precision Medicine: A Comprehensive Guide to RNA Therapeutics.Current issues in molecular biology · 2026Review
- Expanding the toolbox: Emerging antisense oligonucleotide mechanisms for modulating gene expression.Molecular therapy. Nucleic acids · 2026Review
- 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
- Review
- Atrophin-1 antisense oligonucleotide provides robust protection from pathology in a fully humanized DRPLA model.Molecular therapy. Nucleic acids · 2026Article
- Unraveling the mechanisms of slack channel mutations in epileptic disorders.Acta epileptologica · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Expanding the phenotypic and genotypic spectrum ofBrain communications · 2026Article
- Genetic medicines for epilepsy: unlocking new avenues for seizure control.Frontiers in bioengineering and biotechnology · 2026Review
- Transgenic mouse models of sodium and potassium channelopathies in epilepsy: insights into disease mechanisms and therapeutics.Bioscience reports · 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
- Article
- Natural History of NAA15 -Related Neurodevelopmental Disorder Through Adolescence.American journal of medical genetics. Part A · 2025Article
- Systematic analysis of genetic and phenotypic characteristics reveals antisense oligonucleotide therapy potential for one-third of neurodevelopmental disorders.Genome medicine · 2025Article
- Overgrowth-intellectual disability disorders: progress in biology, patient advocacy and innovative therapies.Disease models & mechanisms · 2025Review
- The N=1 Collaborative: advancing customized nucleic acid therapies through collaboration and data sharing.Nucleic acids research · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Developmental and epileptic encephalopathies (DEEs) are characterized by pharmaco-resistant seizures with concomitant intellectual disability. Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the most severe of these syndromes. De novo variants in ion channels, including gain-of-function variants in KCNT1, which encodes for sodium activated potassium channel protein KNa1.1, have been found to play a major role in the etiology of EIMFS. Here, we test a potential precision therapeutic approach in KCNT1-associated DEE using a gene-silencing antisense oligonucleotide (ASO) approach. We generated a mouse model carrying the KCNT1 p.P924L pathogenic variant; only the homozygous animals presented with the frequent, debilitating seizures and developmental compromise that are seen in patients. After a single intracerebroventricular bolus injection of a Kcnt1 gapmer ASO in symptomatic mice at postnatal day 40, seizure frequency was significantly reduced, behavioral abnormalities improved, and overall survival was extended compared with mice treated with a control ASO (nonhybridizing sequence). ASO administration at neonatal age was also well tolerated and effective in controlling seizures and extending the life span of treated animals. The data presented here provide proof of concept for ASO-based gene silencing as a promising therapeutic approach in KCNT1-associated epilepsies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.