{
  "id": 15433671,
  "title": "A Humanized Mouse Model of DRPLA Recapitulates Epilepsy and Demonstrates Antisense Oligonucleotide-Mediated Disease Modification",
  "url": "https://urgent.news/2026/10/18/a-humanized-mouse-model-of-drpla-recapitulates-epilepsy-and",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-18T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758592v1?rss=1"
  },
  "original_language": "en",
  "account": "A humanized mouse model of Dentatorubral-pallidoluysian atrophy (DRPLA) has been developed to study the effects of a disease-causing mutation on epilepsy. DRPLA is a rare genetic disorder caused by an abnormal expansion of CAG repeats in the atrophin-1 (ATN1) gene, leading to progressive myoclonus epilepsy. In this study, researchers engineered an ATN1 mouse with 112 CAG repeats, mimicking the human disease, and compared it to wild-type mice. The Atn1Q112/+ mice exhibited higher seizure susceptibility, early death, and ataxia compared to the WT mice. However, when treated with an experimental antisense oligonucleotide (ASO) targeting the human, CAG-expanded ATN1 gene, the seizure threshold was normalized, ataxia was reduced, and early death was prevented. The ASO-treated mice also showed improvement in seizure-related brain wave patterns (EEG) and behavioral seizures. These findings suggest that the ATN1 mouse model is a valuable tool for studying DRPLA epilepsy and could potentially be used to investigate new therapeutic approaches for this rare and debilitating condition.",
  "summary": "Dentatorubral-pallidoluysian atrophy (DRPLA) is an ultra-rare progressive myoclonus epilepsy caused by a glutamine-coding CAG repeat expansion in atrophin-1 (ATN1). Mutant ATN1 (mATN1) expression results in symptoms that inversely correlate to CAG-expansion size: young-onset cases have the most CAG repeats and developmental delay, high-frequency treatment-resistant seizures, and early mortality.…",
  "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."
}