{
  "abstract": "Pantothenate kinase-associated neurodegeneration (PKAN) is a rare progressive neurodegenerative disorder associated with iron accumulation in the brain. The disease, which causes early immobility and often death by early adulthood, is caused by loss of function mutations in the human PANK2 gene, encoding a key enzyme in the biosynthesis of coenzyme A from pantothenic acid. To date, no disease-modifying therapy exists for PKAN, and current interventions are largely limited to symptomatic management. Herein, we report the identification of a new class of direct activators of human PANK3, termed VTACs, designed to compensate for the loss of PANK2 function. Using cellular and mouse models of PKAN, we demonstrate that a lead VTAC compound, VTAC-2, increases coenzyme A levels in PanK2-deficient cells and in the globus pallidus and substantia nigra, two brain regions prominently affected in PKAN patients. Moreover, the favorable physicochemical properties and oral bioavailability of VTAC-2 make this compound an attractive candidate for clinical evaluation for the treatment of PKAN.",
  "abstract_shown": true,
  "affiliations": [
    "Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA",
    "Virtus Therapeutics Corporation, Groton, Connecticut, USA",
    "Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, USA",
    "Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jessica Regan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anasuya C. Pal"
    },
    {
      "affs": [
        0
      ],
      "name": "Shalev Gihaz"
    },
    {
      "affs": [
        0
      ],
      "name": "Richard E. Sutton"
    },
    {
      "affs": [
        0,
        2,
        3
      ],
      "name": "Choukri Ben Mamoun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3h4xe3yevwnca.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jbc.2026.113567",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13717179/",
  "id": "3h4xe3yevwnca",
  "issns": [
    "0021-9258",
    "1083-351X"
  ],
  "landing_url": "https://doi.org/10.1016/j.jbc.2026.113567",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2808|Neurological diseases and metabolism"
    ]
  ],
  "openalex": "W7213468438",
  "pdf_url": null,
  "pmcid": "PMC13717179",
  "pmid": "42754166",
  "published": "2026-09-17",
  "publisher": "American Society for Biochemistry and Molecular Biology",
  "ris": "https://research.draconitic.com/paper/3h4xe3yevwnca.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:21:32Z",
      "native_id": "PMC13717179",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jbc.2026.113567"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neurological diseases and metabolism",
      "subfield": "neurology"
    }
  ],
  "title": "A selective PanK3 activator increases coenzyme A levels in cellular and mouse models of pantothenate kinase-associated neurodegeneration",
  "title_text": "A selective PanK3 activator increases coenzyme A levels in cellular and mouse models of pantothenate kinase-associated neurodegeneration",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:32Z",
  "url": "https://research.draconitic.com/paper/3h4xe3yevwnca",
  "venue": "The Journal of Biological Chemistry",
  "versions": []
}