PURPOSE: We sought to investigate the safety and efficacy of intramuscular gene therapy with vascular endothelial growth factor (VEGF) in patients with chronic critical leg ischemia. METHODS: Gene transfer was performed in 24 limbs of 21 patients with rest pain, some of whom also had nonhealing ischemic ulcers (n = 16) due to occlusive peripheral arterial disease. Between 400 μg and 2000 μg of phVEGF165 (400 μg, n = 2; 800 μg, n = 4; 1200 μg, n = 4; 1600 μg, n = 6; and 2000 μg, n = 8) was injected directly into the muscles of the ischemic limb; the same dose was injected 4 weeks later. The ratio of blood pressures at the ankle and brachial artery was measured before and after treatment. RESULTS: Mean (± SD) plasma levels of VEGF increased significantly from 26 ± 31 pg/mL to 63 ± 56 pg/mL (P <0.005), and the ankle-brachial index improved significantly from 0.58 ± 0.24 to 0.72 ± 0.28 (P <0.001). Magnetic resonance angiography showed qualitative evidence of improved distal flow in 19 limbs (79%). Ischemic ulcers healed or improved markedly in 12 limbs (75%). Rest pain was relieved or improved markedly in 20 limbs (83%). Amputation was performed in two limbs because of wound infection. Complications were limited to transient leg edema in six limbs. CONCLUSION: Intramuscular gene therapy with VEGF165 for patients with chronic critical leg ischemia is safe, feasible, and effective.
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