Gene Therapy in Cardiac Disease

Abstract

To date, over 1000 patients have been enrolled in clinical trials of gene therapy for heart disease (either coronary artery disease or heart failure). Gene transfer has been associated with an excellent safety profile so far, regardless of vector or delivery methods. However, therapeutic efficacy has been underwhelming; large pivotal, randomized, placebo-controlled trials have failed to reproduce the efficacy signals observed in earlier-phase clinical testing, and primary endpoints have not been met. Importantly, low efficiency of gene transfer into cardiomyocytes appears to remain a significant obstacle. Moving forward, research efforts should focus on development of better vectors, more efficient delivery systems, deeper understanding of disease pathophysiology, and improved clinical trial design (including selection of appropriate dosages, patients, and endpoints). In this chapter, we first touch upon the basic principles of gene transfer for cardiac disease, including discussion of different vectors and delivery methods. We then critically review gene-based therapeutic interventions that have been tested clinically in patients, primarily focusing on randomized, placebo-controlled clinical trials.