Wolf CM, Zenker M, Boleti O, Norrish G, Russell M, Meisner JK, Peng DM, Prendiville T, Kleinmahon J, Kantor PF, Sen DG, Human DG, Ewert P, Krueger M, Reber D, Donner B, Hart C, Komazec IO, Rupp S, Hahn A, Hanser A, Hofbeck M, Draaisma JMT, Cate FEAUT, Mussa A, Ferrero GB, Vaujois L, Raboisson MJ, Delrue MA, Marquis C, Theoret Y, Bogarapu S, Dancea A, Handrup MM, Kemna M, Ojala T, Dham N, Dicke F, Friede T, Kaski JP, Gelb BD, Andelfinger G
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. (JACC Basic Transl Sci. 2025;10:152-166) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
