Prospects for gene therapy for heart failure

Heart failure represents an enormous clinical challenge in need of effectiv e therapeutic approaches, The possibility of gene therapy for heart failure merits consideration at this time because of improvements in vector techno logy; cardiac gene delivery; and, most importantly, our understanding of th e molecular pathogenesis of heart Failure. We will first review recent adva nces in cardiac gene delivery in animal models and then examine several tar gets being considered for therapeutic intervention. In this context, gene t ransfer provides not only a potential therapeutic modality but also an impo rtant tool to help validate specific targets. Several interventions, partic ularly those enhancing sarcoplasmic calcium transport, show promise in anim al models of heart failure and in myopathic cardiomyocytes derived from pat ients. However, bridging the gap between these basic investigative studies and clinical gene therapy remains a formidable task. Early experiments in r odents will need to be extended to large-animal models with clinical-grade vectors and delivery systems to assess both efficacy and safety. On the bas is of a foundation of rigorous science and a growing understanding of heart failure pathogenesis, there is reason for cautious optimism for the future .