期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 31, 期 3, 页码 713-720出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.110.219550
关键词
gene therapy; growth factors; peripheral arterial disease
资金
- National Institute of Biomedical Innovation
- Organization for Pharmaceutical Safety and Research
- Ministry of Public Health and Welfare
- Japan Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology, Japanese government
Objective-To evaluate the safety and feasibility of intramuscular gene transfer using naked plasmid DNA-encoding hepatocyte growth factor (HGF) and to assess its potential therapeutic benefit in patients with critical limb ischemia. Methods and Results-Gene transfer was performed in 22 patients with critical limb ischemia by intramuscular injection of HGF plasmid, either 2 or 4 mg, 2 times. Safety, ankle-brachial index, resting pain on a 10-cm visual analog scale, wound healing, and walking distance were evaluated before treatment and at 2 months after injection. No serious adverse event caused by gene transfer was detected over a follow-up of 6 months. Of particular importance, no peripheral edema, in contrast to that seen after treatment with vascular endothelial growth factor, was observed. In addition, the systemic HGF protein level did not increase during the study. At 2 months after gene transfer, the mean +/- SD ankle-brachial index increased from 0.46 +/- 0.08 to 0.59 +/- 0.13 (P<0.001), the mean +/- SD size of the largest ischemic ulcers decreased from 3.08 +/- 1.54 to 2.32 +/- 1.88 cm (P=0.007), and the mean +/- SD visual analog scale score decreased from 5.92 +/- 1.67 to 3.04 +/- 2.50 cm (P=0.001). An increase in ankle-brachial index by >0.1, a reduction in ulcer size by >25%, and a reduction in visual analog scale score by >2 cm at 2 months after gene transfer were observed in 11 (64.7%) of 17 limbs, 18 (72%) of 25 ulcers, and 8 (61.5%) of 13 limbs, respectively. Conclusion-Intramuscular injection of naked HGF plasmid is safe and feasible and can achieve successful improvement of ischemic limbs as sole therapy. (Arterioscler Thromb Vasc Biol. 2011;31:713-720.)
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