Open AccessNovel Therapies for Prevention and Early Treatment of Cardiomyopathies
Author(s) -
Giuliana G. Repetti,
Christopher N. Toepfer,
Jonathan G. Seidman,
Christine E. Seidman
Publication year - 2019
Publication title -
circulation research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.899
H-Index - 336
eISSN - 1524-4571
pISSN - 0009-7330
DOI - 10.1161/circresaha.119.313569
Subject(s) - haploinsufficiency , mechanism (biology) , cardiomyopathy , medicine , heart failure , disease , bioinformatics , allele , heart disease , gene , biology , genetics , phenotype , philosophy , epistemology
Heritable cardiomyopathies are a class of heart diseases caused by variations in a number of genetic loci. Genetic variants on one allele lead to either a degraded protein, which causes a haploinsufficiency of that protein, or a nonfunctioning protein that subverts the molecular system within which the protein works. Over years, both of these mechanisms eventually lead to diseased heart tissue and symptoms of a failing heart. Most cardiomyopathy treatments repurpose heart failure drugs to manage these symptoms and avoid adverse outcomes. There are few therapies that correct the underlying pathogenic genetic or molecular mechanism. This review will reflect on this unmet clinical need in genetic cardiomyopathies and consider a variety of therapies that address the mechanism of disease rather than patient symptoms. These therapies are genetic, targeting a defective gene or transcript, or ameliorating a genetic insufficiency. However, there are also a number of small molecules under exploration that modulate downstream faulty protein products affected in cardiomyopathies.