Gene therapy for the treatment of heart failure: promise postponed

Abstract

Gene therapy has emerged as a powerful tool in targeting the molecular mechanisms implicated in heart failure. Refinements in vector technology, including the development of recombinant adeno-associated vectors, have allowed for safe, long-term, and efficient gene transfer to the myocardium. These advancements, coupled with evolving delivery techniques, have placed gene therapy as a viable therapeutic option for patients with heart failure. However, after much promise in early-phase clinical trials, the more recent larger clinical trials have shown disappointing results, thus forcing the field to re-evaluate current vectors, delivery systems, targets, and endpoints. We provide here an updated review of current cardiac gene therapy programmes that have been or are being translated into clinical trials.

Keywords: Adeno-associated vectors; Excitation–contraction coupling; Gene therapy; Heart failure; Sarcoplasmic reticulum calcium ATPase.

Figure 1

Representative vectors used for cardiac gene therapy.

Figure 2

Methods of myocardial targeted gene delivery. (A) Antegrade intracoronary injection. (B) Retrograde injection through the coronary sinus with simultaneous blockade of the antegrade flow. (C and D) Direct myocardial injections through the left ventricle using catheter-based and surgical approach. (E) Intrapericardial injection.