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International Angiology 2011 April;30(2):140-9


language: English

Transfection of human HGF plasmid DNA improves limb salvage in Buerger’s disease patients with critical limb ischemia

Shigematsu H. 1, Yasuda K. 2, Sasajima T. 3, Takano T. 4, Miyata T. 5, Ohta T. 6, Tanemoto K. 7, Obitsu Y. 1, Iwai T. 8, Ozaki S. 9, Ogihara T. 10, Morishita R. 11

1 Department of Vascular Surgery, Tokyo Medical University, Tokyo, Japan; 2 Hokkaido Chuo Rosai Hospital Spinal Cord Injury Center, Japan Labour Health and Welfare Organization, Hokkaido, Japan; 3 First Department of Surgery, Asahikawa Medical University, Hokkaido, Japan; 4 First Department of Internal Medicine, Nihon Medical School, Tokyo, Japan; 5 Division of Vascular Surgery, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; 6 Department of Vascular Surgery, Aichi Medical University, Aichi, Japan; 7 Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Kawasaki Medical School, OkayamaJapan 8 Tsukuba Vascular Center and Buerger’s Disease Research Institute (NPO), Moriya Keiyu Hospital, Ibaraki, Japan 9 Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan 10 Osaka General Medical Center, Osaka, Japan 11 Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Osaka, Japan


AIM: Hepatocyte growth factor is a potent angiogenic agent. This study investigated the efficacy and safety of intramuscular injection of naked plasmid DNA encoding the human hepatocyte growth factor gene in Japanese patients with Buerger’s disease and critical limb ischemia.
METHODS: An open-label clinical study was performed at eight hospitals in Japan from May 2004 to April 2008. Ten patients were enrolled. They had Buerger’s disease with ischemic ulcers, were not candidates for revascularization, and were unresponsive to conventional drug therapy. Treatment consisted of 8 injections (total dose: 4 mg) of hepatocyte growth factor plasmid, which were administered into the calf muscles and/or distal thigh muscles of the ischemic limbs under ultrasound guidance. Administration was done twice at an interval of 4 weeks. If there was no improvement after 2 doses, a 3rd dose could be administered. The response to treatment was evaluated from the reduction of ischemic ulcer size.
RESULTS: The size of ischemic ulcers showed a decrease in 6/9 (66.7%) patients and the ulcers healed completely in 5/9 (55.6%) patients after gene therapy. Major amputation was not required. There were no deaths and no major safety concerns.
CONCLUSION: Hepatocyte growth factor gene therapy is safe and effective for critical limb ischemia in patients with Buerger’s disease.

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