Impact of MEK Inhibition on Childhood RASopathy-Associated Hypertrophic Cardiomyopathy

authored by

Cordula M. Wolf, Martin Zenker, Olga Boleti, Gabrielle Norrish, Mark Russell, Joshua K. Meisner, David M. Peng, Terence Prendiville, Jake Kleinmahon, Paul F. Kantor, Danielle Gottlieb Sen, Derek G. Human, Peter Ewert, Marcus Krueger, Daniela Reber, Birgit Donner, Christopher Hart, Irena Odri Komazec, Stefan Rupp, Andreas Hahn, Anja Hanser, Michael Hofbeck, Jos M.T. Draaisma, Floris E.A. Udink ten Cate, Alessandro Mussa, Giovanni B. Ferrero, Laurence Vaujois, Marie Josée Raboisson, Marie Ange Delrue, Christopher Marquis, Yves Théoret, Soujanya Bogarapu, Adrian Dancea, Mette Moller Handrup, Mariska Kemna, Tiina Ojala, Niti Dham, Frank Dicke, Tim Friede, Juan Pablo Kaski, Bruce D. Gelb, Gregor Andelfinger

Abstract

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.

External Organisation(s)

Technical University of Munich (TUM)
German Centre for Cardiovascular Research
ERN GUARD-Heart
Otto-von-Guericke University Magdeburg
University College London (UCL)
Great Ormond Street Hospital for Children NHS Trust
University of Michigan
Our Lady's Hospital for Sick Children
Ochsner Hospital for Children
University of Southern California
Johns Hopkins University
University of British Columbia
München Klinik Bogenhausen
University of Basel
University of Bonn
Innsbruck Medical University
University Hospital Gießen and Marburg
Justus Liebig University Giessen
University of Tübingen
Radboud University Nijmegen (RU)
University of Turin
Universite Laval
University of Montreal
University of Illinois at Chicago
McGill University Health Center
Aarhus University
Seattle Children's Hospital
University of Helsinki
Children's National Medical Center
University of Calgary
University of Göttingen
German Center for Child and Adolescent Health (DZKJ)
Icahn School of Medicine at Mount Sinai (ISMMS)

Type

Article

Journal

JACC: Basic to Translational Science

Volume

10

Pages

152-166

No. of pages

15

ISSN

2452-302X

Publication date

02.2025

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

Electronic version(s)

https://doi.org/10.1016/j.jacbts.2024.10.002 (Access: Open)