Mechanism based therapies enable personalised treatment of hypertrophic cardiomyopathy.

ABSTRACT: Cardiomyopathies have unresolved genotype-phenotype relationships and lack disease-specific treatments. Here we provide a framework to identify genotype-specific pathomechanisms and therapeutic targets to accelerate the development of precision medicine. We use human cardiac electromechanical in-silico modelling and simulation which we validate with experimental hiPSC-CM data and modelling in combination with clinical biomarkers. We select hypertrophic cardiomyopathy as a challenge for this approach and study genetic variations that mutate proteins of the thick (MYH7^R403Q/+) and thin filaments (TNNT2^R92Q/+, TNNI3^R21C/+) of the cardiac sarcomere. Using in-silico techniques we show that the destabilisation of myosin super relaxation observed in hiPSC-CMs driv

SUBMITTER: Margara F 

PROVIDER: S-EPMC9797561 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature