Neoangiogenesis by local gene therapy: a new therapeutic approach in the treatment of coronary artery disease

This article presents the results of our initial clinical experience with t he human growth factor FGF-1 as applied to the ischemic human myocardium. After the completion of extensive preliminary animal experiments, the human angiogenetic growth factor FGF-1, obtained from a genetically transformed strain of E. coli was introduced into aortocoronary bypass surgery as an ad ditional therapeutic agent. A double-blind study was carried out in a total of 40 patients with coronary heart disease. The patients were randomized i nto growth-factor and control groups, each containing 20 patients. All pati ents underwent aortocoronary bypass surgery because of their coronary multi vessel disease, in each case with an IMA bypass for the LAD and single veno us bypasses for the RCX and/or RCA. In order to bridge over additional sten osis of the LAD or one of its branches, the human growth factor FGF-1 was i njected into the myocardium during the operation. In the control group heat -denatured growth factor was substituted for FGF-1. After three months as w ell as three years postoperatively, the IMA bypasses were selectively depic ted by intraarterial DSA. These angiographies were then guantitatively eval uated. After the application of the growth factor, the formation of new ves sels could be demonstrated after three months as well as three years postop eratively. A capillary network initiating from the coronary artery could be found and the computer-supported evaluation of the angiographs revealed a significant increase in the blued supply of the region of the myocardium in jected. According to the angiographic findings there was also a clinical im provement of the patients with FGF-1 application compared to the patients o f control group, concerning the NYHA classification as well as the need for antiangina drug therapy. In the meantime, the results of other research groups support the evidence that the induction of neoangiogenesis by human growth factor could become a therapeutic approach especially in patients with diffuse coronary artery d isease. Nevertheless further studies have to be carried out in order to pro ve the long-term clinical profit of those patients after the growth factor treatment.