Cellular models and therapeutic perspectives in hypertrophic cardiomyopathy

TL;DR

This paper reviews cellular models for hypertrophic cardiomyopathy and explores their potential for developing personalized therapies.

Contribution

The paper provides an updated review of cellular and tissue-based models for HCM and outlines future therapeutic strategies.

Findings

HCM is genetically heterogeneous with pathogenic variants in over 20 genes.

Cellular models help uncover causative genetic alterations and support therapeutic development.

Tissue-engineered models are valuable for drug screening and genome editing approaches.

Abstract

Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous cardiac disease that is mainly characterized by left ventricular hypertrophy in the absence of any additional cardiac or systemic disease. HCM is genetically heterogeneous, inherited mainly in an autosomal dominant pattern, and so far pathogenic variants have been identified in more than 20 genes, mostly encoding proteins of the cardiac sarcomere. Based on its variable penetrance and expressivity, pathogenicity of newly identified variants often remains unsolved, underlining the importance of cellular and tissue-based models that help to uncover causative genetic alterations and, additionally, provide appropriate systems for the analysis of disease hallmarks as well as for the design and application of new therapeutic strategies like drug screenings and genome/base editing approaches. Here, we review the current state of cellular and tissue-engineered models and provide future perspectives for personalized therapeutic strategies of HCM.