Angiogenic Gene Therapy in Patients with Ischemic Cardiovascular Diseases

ABSTRACT

Coronary artery disease (CAD) and peripheral vascular disease (PVD) are significant medical problems worldwide, including Korea. Although substantial progress has been made in prevention and treatment of these diseases, particularly CAD, there are still a large number of patients, who despite maximal medical treatment have substantial symptomatology, so are not suitable for mechanical revascularization. Therapeutic angiogenesis represents a novel, conceptually appealing, treatment option for these patients. Consequently, there are several different products in clinical trials looking at the various angiogenic growth factors. A number of small, mostly open-labeled phase I or I/II, studies have been conducted with adeno- and plasmid-based vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) gene constructs in CAD and PVD. Although these studies have provided intriguing indications of the possibility of new vessel formation, and that these new vessels could be functional, these studies have been too small to allow definite conclusions on their potential efficacy to be drawn. Although, larger scale placebo-controlled studies of gene transfer are in progress. Future clinical studies will be required to determine the optimal dose, formulation, route of administration and combination of growth factors, as well as the requirement for endothelial progenitor cell, or stem cell supplementation, to provide effective and safe therapeutic angiogenesis. This exciting new field is reviewed, with special emphasis on clinical trials.