{
  "abstract": "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. We sought to characterize the seizure susceptibility of a fully humanized ATN1 mouse expressing human mATN1 with 112 CAG repeats to then assess therapeutic antisense oligonucleotide (ASO) intervention on seizure-related outcomes. Atn1Q112/+ or wild-type (WT) mice were treated with investigational ASO targeting human, CAG-expanded, ATN1 or saline (P2 and then again at 4 weeks-old) before acute seizure testing, ataxia profiling, and chronic in vivo video-EEG recording for spontaneous seizures up to 8 weeks-old. Saline-treated Atn1Q112/+ mice were more seizure prone with early death. However, ASO administration to Atn1Q112/+ mice normalized seizure threshold, decreased ataxia, and protected against early death. Atn1Q112/+ mice exhibited spontaneous behavioral seizures recorded over 2 weeks, which were absent in ASO-treated Atn1Q112/+ and WT mice, with a specific mATN1 expression-driven decrease in delta and theta EEG frequencies. Atn1Q112/+ mice are highly seizure prone, validating this model for DRPLA epilepsy. ATN1 represents a novel epilepsy-related risk factor for therapeutic investigation.",
  "abstract_shown": true,
  "affiliations": [
    "mhaliski@uw.edu"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Q. WU"
    },
    {
      "name": "I. Erickson"
    },
    {
      "name": "S. Davidson"
    },
    {
      "name": "S. Shonka"
    },
    {
      "name": "V. Smith"
    },
    {
      "name": "B. Gidi"
    },
    {
      "name": "K. Knox"
    },
    {
      "name": "T. W. Yu"
    },
    {
      "name": "V. Khurana"
    },
    {
      "name": "J. Carroll"
    },
    {
      "name": "J. A. Korecka"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Barker-Haliski"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9q2hhk6f8rhsd.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.12.758592",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758592v1.full",
  "id": "9q2hhk6f8rhsd",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758592v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2804|Genetic Neurodegenerative Diseases"
    ]
  ],
  "openalex": "W7222881084",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758592v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9q2hhk6f8rhsd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:24Z",
      "native_id": "10.64898/2026.10.12.758592",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.12.758592v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "A Humanized Mouse Model of DRPLA Recapitulates Epilepsy and Demonstrates Antisense Oligonucleotide-Mediated Disease Modification",
  "title_text": "A Humanized Mouse Model of DRPLA Recapitulates Epilepsy and Demonstrates Antisense Oligonucleotide-Mediated Disease Modification",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:24Z",
  "url": "https://research.draconitic.com/paper/9q2hhk6f8rhsd",
  "venue": "bioRxiv",
  "versions": []
}