Unveiling the Future of Cardiac Care: A Review of Gene Therapy in Cardiomyopathies

Abstract

For years, the treatment of many cardiomyopathies has been solely focused on symptom management. However, cardiomyopathies have a genetic substrate, and directing therapy towards the pathophysiology rather than the epiphenomenon of the disease may be a winning strategy. Gene therapy involves the insertion of genes or the modification of existing ones and their regulatory elements through strategies like gene replacement and gene editing. Recently, gene therapy for cardiac amyloidosis and Duchenne muscular dystrophy has received approval, and important clinical trials are currently evaluating gene therapy methods for rare heart diseases like Friedreich's Ataxia, Danon disease, Fabry disease, and Pompe Disease. Furthermore, favorable results have been noted in animal studies receiving gene therapy for hypertrophic, dilated, and arrhythmogenic cardiomyopathy. This review discusses gene therapy methods, ongoing clinical trials, and future goals in this area.

Keywords: CRISPR/Cas9; adeno-associated virus (AAV); cardiomyopathies; clinical trials in cardiomyopathies; gene editing; gene replacement; gene therapy; transgene expression; vector delivery.

Figure 1

Exploring types of Gene Therapies. (A) illustrates how nonsense, frameshift, and missense mutations can lead to loss-of-function mutations, resulting in the absence of functional proteins. (B) depicts how missense variants often lead to gain-of-function mutations, resulting in proteins that exhibit altered or enhanced activity compared to their wild-type forms.