OBJECTIVE: As angiogenic growth factors can stimulate the development of collateral arteries, a concept called therapeutic angiogenesis, we performed a phase I/IIa open-label clinical trial using intramuscular injection of naked plasmid DNA encoding hepatocyte growth factor (HGF). We reported long-term evaluation of 2 years after HGF gene therapy in 22 patients with severe peripheral arterial disease. METHODS AND RESULTS: Twenty-two patients with peripheral arterial disease or Buerger disease staged by Fontaine IIb (n=7), III (n=4), and IV (n=11) were treated with HGF plasmid, either 2 mg or 4 mg ×2. Increase in ankle-branchial pressure index >0.1 was observed in 11 of 14 patients (79 %) at 2 years after gene therapy and in 11 of the 17 patients (65%) at 2 months. Reduction in rest pain (>2 cm in visual analog scale) was observed in 9 of 9 patients (100%) at 2 years and in 8 of 13 (62%) patients at 2 months. At 2 years, 9 of 10 (90%) ischemic ulcers reduced by >25%, accompanied by a reduction in the size of ulcer. Severe complications and adverse effects caused by gene transfer were not detected in any patient throughout the period up to 2 years. CONCLUSIONS: Overall, the present study demonstrated long-term efficacy of HGF gene therapy up to 2 years. These findings may be cautiously interpreted to indicate that intramuscular injection of naked HGF plasmid is safe, feasible, and can achieve successful improvement of ischemic limbs as sole therapy.
OBJECTIVE: As angiogenic growth factors can stimulate the development of collateral arteries, a concept called therapeutic angiogenesis, we performed a phase I/IIa open-label clinical trial using intramuscular injection of naked plasmid DNA encoding hepatocyte growth factor (HGF). We reported long-term evaluation of 2 years after HGF gene therapy in 22 patients with severe peripheral arterial disease. METHODS AND RESULTS: Twenty-two patients with peripheral arterial disease or Buerger disease staged by Fontaine IIb (n=7), III (n=4), and IV (n=11) were treated with HGF plasmid, either 2 mg or 4 mg ×2. Increase in ankle-branchial pressure index >0.1 was observed in 11 of 14 patients (79 %) at 2 years after gene therapy and in 11 of the 17 patients (65%) at 2 months. Reduction in rest pain (>2 cm in visual analog scale) was observed in 9 of 9 patients (100%) at 2 years and in 8 of 13 (62%) patients at 2 months. At 2 years, 9 of 10 (90%) ischemic ulcers reduced by >25%, accompanied by a reduction in the size of ulcer. Severe complications and adverse effects caused by gene transfer were not detected in any patient throughout the period up to 2 years. CONCLUSIONS: Overall, the present study demonstrated long-term efficacy of HGF gene therapy up to 2 years. These findings may be cautiously interpreted to indicate that intramuscular injection of naked HGF plasmid is safe, feasible, and can achieve successful improvement of ischemic limbs as sole therapy.
Authors: Cecilia Berardi; Christine L Wassel; Paul A Decker; Nicholas B Larson; Phillip S Kirsch; Mariza de Andrade; Michael Y Tsai; James S Pankow; Michele M Sale; Hugues Sicotte; Weihong Tang; Naomi Q Hanson; Mary M McDermott; Michael H Criqui; Michael A Allison; Suzette J Bielinski Journal: Angiology Date: 2016-07-20 Impact factor: 3.619
Authors: Cassie J Liu; Douglas S Jones; Ping-Chuan Tsai; Abhishek Venkataramana; Jennifer R Cochran Journal: FEBS Lett Date: 2014-11-21 Impact factor: 4.124
Authors: Kristin M Poole; Jason M Tucker-Schwartz; Wesley W Sit; Alex J Walsh; Craig L Duvall; Melissa C Skala Journal: Am J Physiol Heart Circ Physiol Date: 2013-08-16 Impact factor: 4.733
Authors: Maarten A Lijkwan; Alwine A Hellingman; Ernst J Bos; Koen E A van der Bogt; Mei Huang; Nigel G Kooreman; Margreet R de Vries; Hendrika A B Peters; Robert C Robbins; Jaap F Hamming; Paul H A Quax; Joseph C Wu Journal: Hum Gene Ther Date: 2014-01-07 Impact factor: 5.695