This Article Full Text Full Text (PDF) Data Supplement Correction (v48,pe7) All Versions of this Article: 44/2/203    most recent 01.HYP.0000136394.08900.edv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Morishita, R. Articles by Ogihara, T. Search for Related Content PubMed PubMed Citation Articles by Morishita, R. Articles by Ogihara, T. Related Collections Angiogenesis Peripheral vascular disease Gene therapy Other Vascular biology

(Hypertension. 2004;44:203.)
© 2004 American Heart Association, Inc.

Scientific Contributions

Safety Evaluation of Clinical Gene Therapy Using Hepatocyte Growth Factor to Treat Peripheral Arterial Disease

Ryuichi Morishita; Motokuni Aoki; Naotaka Hashiya; Hirofumi Makino; Keita Yamasaki; Junya Azuma; Yoshiki Sawa; Hikaru Matsuda; Yasufumi Kaneda; Toshio Ogihara

From the Department of Geriatric Medicine (R.M., M.A., N.H., H.M., K.Y., J.A., T.O.), Division of Clinical Gene Therapy (R.M.), Department of Surgery (Y.S., H.M.), and Division of Gene Therapy Science (Y.K.), Graduate School of Medicine, Osaka University, Japan.

Correspondence to Ryuichi Morishita, MD, PhD, Professor, Division of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Japan. E-mail morishit{at}cgt.med.osaka-u.ac.jp

Therapeutic angiogenesis using angiogenic growth factors is expected to be a new treatment for patients with critical limb ischemia (CLI). Because hepatocyte growth factor (HGF) has potent angiogenic activity, we investigated the safety and efficiency of HGF plasmid DNA in patients with CLI as a prospective open-labeled clinical trial. Intramuscular injection of naked HGF plasmid DNA was performed in ischemic limbs of 6 CLI patients with arteriosclerosis obliterans (n=3) or Buerger disease (n=3) graded as Fontaine III or IV. The primary end points were safety and improvement of ischemic symptoms at 12 weeks after transfection. Severe complications and adverse effects caused by gene transfer were not detected in any patients. Of particular importance, no apparent edema was observed in any patient throughout the trial. In addition, serum HGF concentration was not changed throughout the therapy period in all patients. In contrast, a reduction of pain scale of more than 1 cm in visual analog pain scale was observed in 5 of 6 patients. Increase in ankle pressure index more than 0.1 was observed in 5 of 5 patients. The long diameter of 8 of 11 ischemic ulcers in 4 patients was reduced >25%. Intramuscular injection of naked HGF plasmid is safe, feasible, and can achieve successful improvement of ischemic limbs. Although the present data are conducted to demonstrate the safety as phase I/early phase IIa, the initial clinical outcome with HGF gene transfer seems to indicate usefulness as sole therapy for CLI.

Key Words: clinical trials • DNA • blood vessels • safety • vascular diseases