Gene therapy for heart failure

Abstract

Although originally mainly envisioned for the treatment of monogenetic diseases, gene therapy has become a promising therapeutic approach for selected polygenetic cardiac disorders. During the past decades, the pathophysiology of a variety of cardiac diseases is better understood, which has paved the way for targeted gene-based interventions directed at key processes in the pathogenesis of myocardial dysfunction and advanced heart failure (HF). Myocardial ischemia is most often due to obstructive coronary disease and percutaneous coronary intervention or coronary artery bypass grafting to restore perfusion together with state-of-the-art medical treatment is the first-line therapy. A significant number of patients, however, will remain symptomatic despite these conventional interventions (referred to as no-option patients) or have severe and diffuse coronary artery damage, not amenable to routine interventions. These no-option patients might benefit from gene therapy aimed at enhancing neovascularization by either angiogenesis or vasculogenesis. Neovascularization is a physiologic endogenous process in response to ischemia, but when insufficient to resolve ischemia, proangiogenic therapies might prove useful.