Change in rest pain assessment by visual analog scale from baseline at 6 months was also significantly improved in the HGF-treated group compared with placebo. Complete ulcer healing at 12 months

occurred in 31% of the HGF group and 0% of the placebo (P = .28). At 12 months, there was no difference between groups in major amputation of the treated limb (29% in HGF group vs. 33% in Inhibitors,research,lifescience,medical placebo group) or mortality (19% in HGF group vs. 17% in placebo group). VIROMED: The purpose of this phase I clinical trial was to evaluate the safety, tolerability, and preliminary efficacy of naked DNA therapy ARRY-162 manufacturer expressing 2 isoforms of hepatocyte growth factor (pCK-HGF-X7) in 22 patients with CLI. Over a 3-month follow-up period, there was a significant reduction

in pain observed, a significant increase in the mean ABI value, Inhibitors,research,lifescience,medical and a significant rise in the mean TcPO2 value on the dorsum of the foot and anterior and posterior calf. Wound healing improvement was observed in the 6 of 9 patients that had an ulcer at baseline.19 Summary: A meta-analysis has shown the efficacy of therapeutic angiogenesis in critical ischemia (odds ratio Inhibitors,research,lifescience,medical [OR] = 2.20; 95% CI = 1.01-4.79; P = 0.046). There was a slightly significantly higher risk of potential nonserious adverse events (edema, hypotension, proteinuria) in treated patients Inhibitors,research,lifescience,medical (OR = 1.81; 95% CI = 1.01-3.38; P = 0.045). However, there were no differences in mortality from any cause, malignancy, or retinopathy.20 Cell Therapy Recent evidence indicates that bone marrow mononuclear cells (BM-MNC) promote collateral vessel formation in patients with severe peripheral arterial disease (PAD). The BM-MNC from patients with CLI have evidence of an impaired phenotype and a Inhibitors,research,lifescience,medical lower number of endothelial progenitor cells compared to normal or those with Buerger’s Disease.21 Multiple strategies have

been employed to mobilize and derive cells to improve the performance of cell therapy in CLI. Table 2 shows the numerous patient series and controlled studies that have been performed in this area and the successful reported clinical mafosfamide outcomes. Table 2 Results of cell therapy for critical limb ischemia. INTRAMUSCULAR BM-MNC: The first large report on the use of BM-MNC in limb ischemia was the Therapeutic Angiogenesis Using Cell Transplantation (TACT) study. Intramuscular injection of autologous bone marrow mononuclear cells resulted in a 3-year amputation-free rate of 60% (95% CI 46–74). There was significant improvement in the leg pain scale and ulcer size, and pain-free walking distance was maintained during at least 2 years after the therapy, although the ABI and TcPO2 value did not significantly change.