Gene Therapy in Heart Failure

Abstract

Heart failure is a chronic condition leading to debilitating symptoms and reduced life expectancy. Several pharmacological therapies which improve symptoms and mortality have been developed over the past 30 years. These therapies are, however, limited in terms of both efficacy and side‐effect profile. Gene therapy represents a fundamental change in the way treatments are developed with the potential to directly target and correct individual molecular abnormalities. These therapies have the potential to offer long‐term beneficial effects from a single treatment and, with direct targeting, less off‐target effects. As with any new therapy, a number of challenges must be overcome before gene therapy can be considered a realistic option to patients with heart failure. Key Concepts Gene therapy could allow direct targeting of molecular abnormalities in patients with heart failure. Preclinical data suggests that in animal models of heart failure, SERCA2a gene therapy significantly improves haemodynamic parameters, reduces arrhythmia risk and corrects molecular abnormalities. Initial clinical data in a small number of patients suggested that SERCA2a gene therapy was beneficial to patients with advanced heart failure. However, a recent study in a larger number of patients was disappointingly neutral. A number of molecular abnormalities exist in the failing myocytes, each of which could represent a potential target to treat heart failure. Gene therapy requires a large financial commitment from pharmaceutical companies and cost is a major limitation to the development of gene therapy products.