{
  "abstract": "Background: Activating mutations in the RAS-MAPK pathway account for ~20% of cases of pediatric hypertrophic cardiomyopathy (HCM) and are associated with poor outcomes. Mavacamten is approved for obstructive HCM; however, patients with RAS-associated HCM have not been included in the clinical trials so far. We aimed to characterize the functional and energetic disturbances in an in vitro RAS-HCM model and evaluate the therapeutic effects of mavacamten. Methods: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) carrying a CRISPR-induced BRAF (p.Thr599Arg) mutation and their isogenic control were studied. Cell size, contractility, and transcriptomics were assessed, while energetics were determined using MitoStress assays, live ATP imaging, and NAD(P)H/FAD autofluorescence. Results: BRAF-mutant hiPSC-CMs showed hypertrophy, hypercontractility, increased mitochondrial cofactor pools, and enhanced maximal respiratory capacity. Despite this, they developed ATP deficiency in response to rapid pacing, suggesting mitochondrial inefficiencies or an overwhelming ATP demand. Mavacamten normalized mitochondrial respiration and excessive ATP consumption, partially restoring energetic balance and highlighting hypercontractility as a major burden in RAS-HCM. Conclusions: BRAF-mutant cardiomyocytes recapitulate the characteristics of HCM in vitro. Mavacamten mitigates dysfunctions and restores energetic balance under stress conditions, indicating it holds potential as a therapeutic option for RASopathy-associated HCM.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Andrea Ruiz-Velasco"
    },
    {
      "name": "Charlène Jouve"
    },
    {
      "name": "Lucille Deshayes"
    },
    {
      "name": "Michael Kohlhaas"
    },
    {
      "name": "Christoph Maack"
    },
    {
      "name": "Jean-Sébastien Hulot"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c7bmyp0z0k4j5.bib",
  "cited_by": 1,
  "doi": "10.1038/s41390-026-05208-9",
  "fulltext_url": null,
  "id": "c7bmyp0z0k4j5",
  "issns": [
    "0031-3998",
    "1530-0447"
  ],
  "landing_url": "https://hal.science/hal-05775537v1",
  "language": "en",
  "licence": "CC-BY-NC-SA-4.0",
  "licence_label": "CC BY-NC-SA 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-sa/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.mhep"
    ],
    [
      "hal",
      "2.sdv.mhep.csc"
    ],
    [
      "openalex",
      "2705|Cardiomyopathy and Myosin Studies"
    ]
  ],
  "openalex": "W4408007316",
  "pdf_url": "https://hal.science/hal-05775537/document",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-22",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/c7bmyp0z0k4j5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:46Z",
      "native_id": "hal-05775537",
      "source": "hal",
      "url": "https://hal.science/hal-05775537v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "hal:2.sdv.mhep.csc",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Mavacamten improves energy balance in a pre-clinical model of RASopathy-associated hypertrophic cardiomyopathy",
  "title_text": "Mavacamten improves energy balance in a pre-clinical model of RASopathy-associated hypertrophic cardiomyopathy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:46Z",
  "url": "https://research.draconitic.com/paper/c7bmyp0z0k4j5",
  "venue": "Pediatric Research",
  "versions": []
}