Six-month assessment of a phase I trial of angiogenic gene therapy for thetreatment of coronary artery disease using direct intramyocardial administration of an adenovirus vector expressing the VEGF121 cDNA

Objective To summarize the 6-month follow-up of a cohort of patients with c linically significant coronary artery disease who received direct myocardia l injection of an E1(-)E3(-) adenovirus (Ad) gene transfer vector (Ad(GV)VE GF121.10) expressing the human vascular endothelial growth factor (VEGF) 12 1 cDNA to induce therapeutic angiogenesis. Background Therapeutic angiogenesis describes a novel approach to the treat ment of vascular occlusive disease that uses the administration of growth f actors known to induce neovascularization of ischemic tissues. Methods Direct myocardial injection of Ad(GV)VEGF121.10 into an area of rev ersible ischemia was carried out in 21 patients as an adjunct to convention al coronary artery bypass grafting (group A, n = 15) or as sole therapy usi ng a minithoracotomy (group B, n = 6). Results No evidence of systemic or cardiac-related adverse events related t o vector administration was observed up to 6 months after therapy. Trends t oward improvement in angina class and exercise treadmill testing at 6-month follow-up in the sole therapy group suggest the effects of this therapy ar e persistent for greater than or equal to 6 months. Conclusions This study suggests that direct myocardial administration of Ad (GV)VEGF121.10 appears to be well tolerated in patients with clinically sig nificant coronary artery disease, initiation of phase II evaluation of this therapy appears warranted.