Background: Adenovirus-mediated angiogenic growth factor gene transfer provides a new therapeutic strategy for treatment of coronary heart disease. Preclinical studies showed that direct intramyocardial injection of recombinant adenovirus with hepatocyte growth factor gene (Ad-HGF) was able to promote neovascularization, improve heart function and abate the area of ischemic myocardia in animal models. However, the safety and therapeutic effect of Ad-HGF were not evaluated in clinical trials.
Patients and methods: A open-label, safety and tolerance trial of Ad-HGF in 18 patients suffering from coronary heart disease was performed. Three groups, each with 6 patients, received 5x10(8) (low dosage), 1.5 x 10(9) (medium dosage) and 5x10(9) (high dosage) pfu of Ad-HGF/person respectively, by direct multipoint injection into the myocardium while accepting coronary artery bypass surgery. The changes of vital symptoms, blood and urea routine analyses, as well as myocardial perfusion before and after treatment were analyzed.
Results: There was no evidence of systemic or cardiac-related adverse events after intramyocardial administration of the Ad-HGF. Myocardial perfusion of the Ad-HGF-injected area was improved in 3 cases of the low-dose group, 5 cases of the medium-dose group, and all of the high-dose group.
Conclusion: These preliminary clinical data indicate that direct intramyocardial administration of Ad-HGF was well tolerated and could improve myocardial perfusion with a dose-effect relationship, encouraging larger and randomized efficacy trials.