Novel Therapies for Prevention and Early Treatment of Cardiomyopathies

Circulation Research - Tập 124 Số 11 - Trang 1536-1550 - 2019
Giuliana G. Repetti1, Christopher N. Toepfer2,3,4, Jonathan G. Seidman5, Christine E. Seidman6,7
1Giuliana G. Repetti From the Department of Genetics, Harvard Medical School, Boston, MA (G.G.R., C.N.T., J.G.S., C.E.S.)
2Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA (C.N.T., C.E.S.)
3Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (C.N.T.)
4Christopher N. Toepfer From the Department of Genetics, Harvard Medical School, Boston, MA (G.G.R., C.N.T., J.G.S., C.E.S.) Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, United Kingdom (C.N.T.) Cardiovascular Division, Brigham and Women's Hospital, Boston, MA (C.N.T., C.E.S.)
5Jonathan G. Seidman From the Department of Genetics, Harvard Medical School, Boston, MA (G.G.R., C.N.T., J.G.S., C.E.S.)
6From the Department of Genetics, Harvard Medical School, Boston, MA (G.G.R., C.N.T., J.G.S., C.E.S.)
7Howard Hughes Medical Institute, Chevy Chase, MD (C.E.S.).

Tóm tắt

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.

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Circulation Research

Tập 124 Số 11

1536-1550

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