title: Gene therapy in peripheral artery disease.
abstract: BACKGROUND
  Despite the remarkable progress of medicine and endovascular procedures for revascularization, patients with critical limb ischemia (CLI) remain at high risk for amputation and often have a low quality of life due to pain and ulcers in the ischemic leg. Thus, a novel strategy for generating new blood vessels in CLI patients without treatment options is vital. Pre-clinical studies and Phase I clinical trials using VEGF and fibroblast growth factor (FGF) demonstrated promising results; however, more rigorous Phase II and III clinical trials failed to demonstrate benefits for CLI patients. Recently, two multicenter, double-blind, placebo-controlled clinical trials in Japan (Phase III) and the USA (Phase II) showed the benefits of hepatocyte growth factor (HGF) gene therapy for CLI patients. Although the number of patients included in these trials was relatively small, these results imply a distinct beneficial function for HGF over other angiogenic growth factors in a clinical setting.
  
  
  METHODS
  In this review, data from Phase I-III clinical trials of gene therapy for patients with peripheral artery disease (PAD) are examined. In addition, the potential mechanisms behind the success or failure of clinical trials are discussed.
  
  
  CONCLUSIONS
  Compared with VEGF and FGF, HGF has a unique molecular effect on inflammation, fibrosis and cell senescence under pathological conditions. These features may explain the clinical benefits of HGF in PAD patients.
authors: Osaka University Graduate School of Medicine, Department of Clinical Gene Therapy , Suita, Osaka 565-0871 , Japan.
authors: Fumihiro
authors: F
authors: Sanada
authors: Yoshiaki
authors: Y
authors: Taniyama
authors: Yasuhiro
authors: Y
authors: Kanbara
authors: Rei
authors: R
authors: Otsu
authors: Yuka
authors: Y
authors: Ikeda-Iwabu
authors: Miguel
authors: M
authors: Carracedo
authors: Hiromi
authors: H
authors: Rakugi
authors: Ryuichi
authors: R
authors: Morishita
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D005346:Fibroblast Growth Factors / Q000008:administration & dosage / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D007511:Ischemia / Q000235:genetics / Q000628:therapy; D058729:Peripheral Arterial Disease / Q000235:genetics* / Q000628:therapy*; D011788:Quality of Life
chemical_list: D005346:Fibroblast Growth Factors; D017228:Hepatocyte Growth Factor
keywords: VEGF; angiogenesis; fibroblast growth factor; gene therapy; hepatocyte growth factor; peripheral artery disease