Gene therapy in heart failure

Despite various therapeutic approaches heart failure remains one of the leading causes of death. Over the last decade we have acquired a greater knowledge of the pathophysiology of heart failure on a molecular level. In addition, tools for cardiac gene delivery have been developed. Therefore, the possibility of gene therapy for heart failure merits consideration at this time. We will first examine several targets that have been considered for therapeutic intervention and then review recent advances in cardiac gene delivery in animal models. Gene transfer represents not only a potential therapeutic modality but also provides an important tool to help validate specific targets. Several approaches, especially those targeting sarcoplasmic reticulum calcium transport, show promise in animal models of heart failure and in myopathic cardiomyocytes derived from patients. It remains a challenge to close the gap between these basic investigations and the clinical use of gene therapy in heart failure. Experiments in rodents will need to be extended to large-animal models to assess the efficacy and safety of vectors and delivery systems. Based on a growing understanding of heart failure pathogenesis and improvement in delivery systems, there is reason for cautious optimism for the future.