Abstract
Gene therapy is emerging as a potential strategy for the treatment of cardiovascular disease such as restenosis after angioplasty, vascular bypass graft occlusion, myocardial infarction, transplant coronary vasculopathy, homozygous familial hypercholesterolemia and cystic fibrosis, for which no known effective therapy exists. Gene therapy requires efficient in vivo gene transfer technology. During the past decade, many gene transfer methods including viral transfer techniques have been developed, and some are being applied clinically in human gene therapy studies. Some aspects of the biology and pathophysiology of the cardiovascular system start to emerge, and then the time is ripe for the introduction of gene therapy to the management of cardiovascular disorders. The first FDA approved human gene therapy protocol started on 14 September, 1990 in ADA deficiency patients. Eight years since the first approval, over 200 active clinical studies of gene therapy are under investigation (1997). In the cardiopulmonary field, 6 protocols (transfer of LDL receptor to hepatocytes, CFTR to lung, Vascular endothelial growth factor to ASO and restenosis after PTCA, antisense c-myc to restenosis, E2F decoy to graft failure) have been approved. Their objectives are generally to evaluate 1)in vivo efficacy, 2) safety, and 3) therapeutic efficacy. As gene therapy becomes a therapeutic reality, the following must be addressed : 1) safety, 2) persistence of gene expression and duration of treatment, and 3) regulation. In the future, we must find ideal and suitable promoters that can be regulated but allow expression of sufficient amounts of the product, (e. g., a "cut-off"system) for effective gene therapy. Although there are still many unresolved issues, human gene therapy for cardiovascular disease is now a reality.
