{
  "id": 19178693,
  "title": "Allele-agnostic KCNH1 suppression rescues gain-of-function developmental epileptic encephalopathy",
  "url": "https://urgent.news/2026/11/09/allele-agnostic-kcnh1-suppression-rescues-gain-of-function",
  "topic": "science",
  "section": "Science",
  "published": "2026-11-09T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764929v1?rss=1"
  },
  "original_language": "en",
  "account": "KCNH1, a gene that encodes the voltage-gated potassium channel Kv10.1, has been linked to gain-of-function variants causing developmental and epileptic encephalopathies (DEEs). These conditions are marked by seizures, developmental delays, and intellectual disability. Surprisingly, the loss of KCNH1 is not only tolerated but also common in humans and mice, indicating that reducing the gene could be an effective treatment for these disorders. Researchers developed an antisense oligonucleotide (ASO) that targets KCNH1 and tested its potential in human iPSC-derived neurons and a mouse model of KCNH1-related disorder. Neurons carrying specific pathogenic variants (I494V or G375R) showed a common symptom: a hyperpolarized resting membrane potential and irregular neuronal network activity, even though their normal firing properties remained largely intact. The ASO treatment proved successful in reducing the expression of KCNH1 without interfering with the network activity in control neurons. However, in mutant neurons, the ASO treatment restored normal network function, suggesting that the diverse KCNH1 gain-of-function variants share a reversible disease state. To further validate the ASO's effectiveness, the researchers created a new Kcnh1-R357Q knock-in mouse model that displayed severe seizures and a shortened lifespan. A single dose of the ASO significantly decreased the seizure activity and extended the mice's survival to near-normal levels. The study concludes that suppressing KCNH1 could serve as a targeted therapeutic approach for KCNH1-related DEEs, offering a model for managing gain-of-function epilepsies where partial gene reduction is generally safe.",
  "summary": "Gain-of-function variants in KCNH1, which encodes the voltage-gated potassium channel Kv10.1, cause developmental and epileptic encephalopathies (DEEs) characterized by seizures, developmental delay and intellectual disability. While pathogenic variants enhance channel activity, loss of KCNH1 is tolerated in humans and mice, suggesting that allele-agnostic gene suppression may represent a viable…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}