2026-07-25T03:51:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/275972026-07-17T00:17:42Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Sen-Martín, Laura
author
Fernández-Trasancos, Ángel
author
López-Unzu, Miguel Á
author
Bak, Agata
author
Zafra-Castellano, Magdalena
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Srikantharajah, Rajiven
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Pathak, Divya
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Klotz, Annika
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Kuehn, Michel N
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Ferrarini, Alessia
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Labrador-Cantarero, Verónica
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Sánchez-Ortiz, David
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Pricolo, María Rosaria
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Vicente, Natalia
author
Velázquez-Carreras, Diana
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Sánchez-García, Lucía
author
Sicilia, Jon
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Nicolás-Ávila, José Ángel
author
Sánchez-Díaz, María
author
Schlossarek, Saskia
author
Cussó, Lorena
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Desco, Manuel
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Villalba-Orero, María
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Guzmán-Martínez, Gabriela
author
Calvo, Enrique
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Barriales-Villa, Roberto
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Vázquez, Jesús
author
Sánchez-Cabo, Fátima
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Hidalgo, Andrés
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de Tombe, Pieter P
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Carrier, Lucie
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Spudich, James A
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Ruppel, Kathleen M
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Weinberger, Florian
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Cazorla, Olivier
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Hessel, Anthony L
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Alegre-Cebollada, Jorge
2026-07-16T10:31:22Z
2026-07-16T10:31:22Z
2026-07
Nat Cardiovasc Res. 2026 Jul;5(7):638-657.
NATURE CARDIOVASCULAR RESEARCH
42414613
https://hdl.handle.net/20.500.12105/27597
Mavacamten is a targeted treatment for hypertrophic cardiomyopathy, a disease caused by genetic variants affecting mainly sarcomeric myosin and its regulator cardiac myosin-binding protein C (cMyBP-C, encoded by MYBPC3). Here we generate knock-in mice including missense pathogenic variant cMyBP-C p.R502W, which unlike carriers of cMyBP-C truncations, develop pathogenic myocardial remodeling with preserved cMyBP-C levels and localization. Mechanistically, R502W reduces cMyBP-C-myosin affinity and generates sarcomere hypercontractility due to increased Ca sensitivity and a favored ON structural state of myosin. Even though these pathomechanisms do not overlap with those triggered by truncating MYBPC3 variants, mavacamten blunts myocardial remodeling both in R502W and cMyBP-C-deficient hearts, correlating with the drug's ability to restore OFF myosin in R502W sarcomeres. In R502W human engineered heart tissues, mavacamten also opposes hypercontractility. Hence, our results indicate that mavacamten is effective in treating hypertrophic cardiomyopathy caused by both truncating and missense MYBPC3 variants regardless of their primary pathomechanisms.
eng
Mavacamten shows broad benefit in human and mouse models of MYBPC3-related hypertrophic cardiomyopathy.
research article
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https://repisalud.isciii.es/bitstreams/6f7557dc-01c3-4538-9a2d-da5a31dd33d7/download
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Mavacamten shows broad benefit in human_Nat Cardiovasc Res_2026.pdf