Gene therapy for myocardial infarction: A real medicine in the next millenium?

Recently, gene therapy has been the center of interest in the treatment of cardiovascular diseases. One of the major targets for gene therapy is myocardial infarction, In this chapter, we discuss two potential gene therapy strategies: (1) replication of dead myocytes by genetically modified cardiac myocytes, and (2) prevention of myocardial infarction by NF kappa B decoy ODN. The use of genetically modified cells for the delivery of recombinant molecules has emerged as a powerful tool for ex vivo gene therapy. For the application of ex vivo gene therapy to cardiac diseases, we examined the potential of cell grafting into the intact heart. Of importance, survival of myocyte grafts was observed in the noninfarcted and border-zone areas but not in the infarcted area. Targeted expression of recombinant molecules in intracardiac grafts could induce a beneficial response in the myocardium. Another potential target is the essential transcription factor, NF kappa B, as NF kappa B plays a pivotal role in the coordinated transactivation of cytokine and adhesion molecule genes. In vivo transfection of NF kappa B decoy digodeoxynudeotides (ODN) into the coronary artery before as well as after reperfusion resulted in a marked decrease in the infarcted area. We have reported the first successful gene therapy for myocardial infarction using NF kappa B decoy ODN. In this chapter, we also discussed the future direction of gene therapy for myocardial infarction.