Impact of MEK Inhibition on Childhood RASopathy-Associated Hypertrophic Cardiomyopathy
There is an unmet medical need to treat patients with severe hypertrophic cardiomyopathy leading to heart failure and death in children carrying pathogenic activating variants in the RAS/mitogen-activated protein kinase pathway. A retrospective analysis of 61 patients provides evidence for decreased mortality and morbidity with improved cardiac status in patients with RASopathy with severe hypertrophic cardiomyopathy receiving mitogen-activated protein kinase kinase inhibition (n = 30) vs those with standard-of-care treatment (n = 31). Side effects were not life threatening and were manageable. The data presented suggest that personalized therapies targeting underlying signaling pathway abnormalities might be effective in critically ill patients with RASopathy warranting clinical investigation.
Authors
- Jake Kleinmahon (ORCID: https://orcid.org/0000-0003-2335-4760)
- Giovanni Battista Ferrero (ORCID: https://orcid.org/0000-0002-3793-5788)
- Marie‐Ange Delrue (ORCID: https://orcid.org/0000-0003-3472-9548)
- Gabrielle Norrish (ORCID: https://orcid.org/0000-0003-2064-237X)
- Jos Draaisma (ORCID: https://orcid.org/0000-0003-4829-6173)
- Martin Zenker (ORCID: https://orcid.org/0000-0003-1618-9269)
- Andreas Hahn (ORCID: https://orcid.org/0000-0003-0235-5211)
- Christopher Marquis
- Cordula M. Wolf (ORCID: https://orcid.org/0000-0003-4701-5843)
- Laurence Vaujois (ORCID: https://orcid.org/0000-0003-4608-5962)
- Joshua K. Meisner (ORCID: https://orcid.org/0000-0003-1049-8351)
- Mariska Kemna (ORCID: https://orcid.org/0000-0001-9484-3006)
- David M. Peng (ORCID: https://orcid.org/0000-0001-7763-7518)
- Tiina Ojala (ORCID: https://orcid.org/0000-0001-9092-7763)
- Floris E.A. Udink ten Cate (ORCID: https://orcid.org/0000-0002-7889-5225)
- Paul F. Kantor (ORCID: https://orcid.org/0000-0002-4244-1563)
- Juan Pablo Kaski (ORCID: https://orcid.org/0000-0002-0014-9927)
- Mette Møller Handrup (ORCID: https://orcid.org/0000-0001-5341-239X)
- Peter Ewert (ORCID: https://orcid.org/0000-0003-0253-1190)
- Michael Hofbeck (ORCID: https://orcid.org/0000-0001-7034-1132)
- Olga Boleti (ORCID: https://orcid.org/0000-0002-0254-0217)
- Tim Friede (ORCID: https://orcid.org/0000-0001-5347-7441)
- Stefan Rupp (ORCID: https://orcid.org/0000-0001-9435-929X)
- Adrian Dancea
- Derek G. Human (ORCID: https://orcid.org/0000-0002-4688-8530)
- Birgit Donner (ORCID: https://orcid.org/0000-0001-8780-1975)
- Irena Odri Komazec
- Niti Dham (ORCID: https://orcid.org/0000-0002-5467-0208)
- Danielle Gottlieb Sen
- Anja Hanser (ORCID: https://orcid.org/0000-0002-7751-8444)
- Soujanya Bogarapu (ORCID: https://orcid.org/0000-0001-9726-582X)
- Marie‐Josée Raboisson (ORCID: https://orcid.org/0000-0002-0850-7063)
- Yves Théorêt (ORCID: https://orcid.org/0000-0002-2353-860X)
- Bruce D. Gelb (ORCID: https://orcid.org/0000-0001-8527-5027)
- Mark W. W. Russell (ORCID: https://orcid.org/0000-0003-4855-9260)
- Grégor Andelfinger (ORCID: https://orcid.org/0000-0002-9047-0502)
- Terence Prendiville (ORCID: https://orcid.org/0000-0002-3824-636X)
- Christopher Hart (ORCID: https://orcid.org/0000-0001-5880-3576)
- Martin Krueger
- Daniela Reber
- Alessandro Mussa
- Frank Dicke
Institutions
- George Washington University Hospital (US)
- Seattle Children's Hospital (US)
- Children's National (US)
- Children's Hospital of Los Angeles (US)
- Innsbruck Medical University (AT)
- Johns Hopkins University (US)
- Radboud University Nijmegen (NL)
- Illinois College (US)
- University of Calgary (CA)
- Justus-Liebig-Universität Gießen (DE)
- Universitätsklinikum Gießen und Marburg (DE)
- University of Michigan (US)
- University Hospital Bonn (DE)
- Johns Hopkins Medicine (US)
- Montreal Children's Hospital (CA)
- Great Ormond Street Hospital (GB)
- Alberta Children's Hospital (CA)
- Centre Hospitalier Universitaire Sainte-Justine (CA)
- Radboud University Medical Center (NL)
- Children's Health Ireland at Crumlin (IE)
- University of Illinois Chicago (US)
- München Klinik Schwabing (DE)
- Radboud Institute for Molecular Life Sciences (NL)
- Child Health and Development Institute (US)
- Amalia Kinderziekenhuis (NL)
- University Children's Hospital Tübingen (DE)
- University Children’s Hospital Basel (CH)
- German Centre for Cardiovascular Research (DE)
- Comer Children's Hospital (US)
- University Hospital Magdeburg (DE)
- ERN GUARD-Heart (NL)
- Pediatrics and Genetics (US)
- Giessen School of Theology (DE)
- Deutsches Herzzentrum München (DE)
- BC Children's Hospital (CA)
- Jefferson Hospital for Neuroscience (US)
- Université Laval (CA)
- University College London (GB)
- University of Turin (IT)
- University of Tübingen (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2024-12-04
- DOI
- https://doi.org/10.1016/j.jacbts.2024.10.002
- Citations
- 17
- Primary Topic
- Cardiomyopathy and Myosin Studies
- Type
- article
- Field-Weighted Citation Impact
- 6.83