Assessment of risks associated with cardiovascular gene therapy in human subjects

Clinical trials of cardiovascular gene therapy, whether using viral (53%) o r nonviral (47%) vectors, have thus far disclosed no evidence indicative of inflammatory or other complications, including death, directly attributabl e to the vector used. Indeed, despite the fact that initial trials of cardi ovascular gene therapy targeted patients with end-stage vascular disease, i ncluding critical limb ischemia and refractory myocardial ischemia, the mor tality for patients enrolled in clinical trials of cardiovascular gene ther apy reported to date compares favorably with mortality for similar groups o f patients in contemporary controlled studies of medical or interventional therapies. The most common morbidity reported after cardiovascular gene tra nsfer is lower extremity edema; in contrast to data involving genetically e ngineered mice, however, evidence of life- or limb-threatening edema has no t been described in any patients, including patients after gene transfer fo r myocardial ischemia. Concerns regarding the potential for angiogenic cyto kines to promote the progression of atherosclerosis are not supported by an giographic follow-up of patients with coronary or peripheral vascular disea se. The levels and duration of gene expression investigated for therapeutic angiogenesis transfer have been unassociated with hemangioma formation. Li kewise, there is little evidence from either preclinical or clinical studie s to support the notion that the administration of angiogenic growth factor s, per se, is sufficient to stimulate the growth of neoplasms. Patients enr olled in clinical studies of angiogenic cytokines, including patients with diabetes and a previous history of retinopathy, have disclosed no evidence to suggest that ocular pathology is a risk of angiogenic growth factor gene transfer.