Clinical trials of cardiovascular gene therapy, whether using viral (53%) or nonviral (47%) vectors, have thus far disclosed no evidence indicative of inflammatory or other complications, including death, directly attributable to the vector used. Indeed, despite the fact that initial trials of cardiovascular gene therapy targeted patients with end-stage
vascular disease, including
critical limb ischemia and refractory
myocardial ischemia, the mortality for patients enrolled in clinical trials of cardiovascular gene therapy reported to date compares favorably with mortality for similar groups of patients in contemporary controlled studies of medical or interventional
therapies. The most common morbidity reported after cardiovascular gene transfer is lower extremity
edema; in contrast to data involving genetically engineered mice, however, evidence of life- or limb-threatening
edema has not been described in any patients, including patients after gene transfer for
myocardial ischemia. Concerns regarding the potential for angiogenic
cytokines to promote the progression of
atherosclerosis are not supported by angiographic follow-up of patients with coronary or
peripheral vascular disease. The levels and duration of gene expression investigated for therapeutic angiogenesis transfer have been unassociated with
hemangioma formation. Likewise, there is little evidence from either preclinical or clinical studies to support the notion that the administration of angiogenic
growth factors, per se, is sufficient to stimulate the growth of
neoplasms. Patients enrolled 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.