title: Transfection of human HGF plasmid DNA improves limb salvage in Buerger's disease patients with critical limb ischemia.
abstract: OBJECTIVE
  Hepatocyte growth factor is a potent angiogenic agent. This study investigated the efficacy and safety of intramuscular injection of naked plasmid DNA encoding the human hepatocyte growth factor gene in Japanese patients with Buerger's disease and critical limb ischemia.
  
  
  METHODS
  An open-label clinical study was performed at eight hospitals in Japan from May 2004 to April 2008. Ten patients were enrolled. They had Buerger's disease with ischemic ulcers, were not candidates for revascularization, and were unresponsive to conventional drug therapy. Treatment consisted of 8 injections (total dose: 4 mg) of hepatocyte growth factor plasmid, which were administered into the calf muscles and/or distal thigh muscles of the ischemic limbs under ultrasound guidance. Administration was done twice at an interval of 4 weeks. If there was no improvement after 2 doses, a 3rd dose could be administered. The response to treatment was evaluated from the reduction of ischemic ulcer size.
  
  
  RESULTS
  The size of ischemic ulcers showed a decrease in 6/9 (66.7%) patients and the ulcers healed completely in 5/9 (55.6%) patients after gene therapy. Major amputation was not required. There were no deaths and no major safety concerns.
  
  
  CONCLUSIONS
  Hepatocyte growth factor gene therapy is safe and effective for critical limb ischemia in patients with Buerger's disease.
authors.affiliation: Department of Vascular Surgery, Tokyo Medical University, Japan. hshige@tokyo-med.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Shigematsu
authors.forename: K
authors.initials: K
authors.lastname: Yasuda
authors.forename: T
authors.initials: T
authors.lastname: Sasajima
authors.forename: T
authors.initials: T
authors.lastname: Takano
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: K
authors.initials: K
authors.lastname: Tanemoto
authors.forename: Y
authors.initials: Y
authors.lastname: Obitsu
authors.forename: T
authors.initials: T
authors.lastname: Iwai
authors.forename: S
authors.initials: S
authors.lastname: Ozaki
authors.forename: T
authors.initials: T
authors.lastname: Ogihara
authors.forename: R
authors.initials: R
authors.lastname: Morishita
mesh_terms: D000328:Adult; D016638:Critical Illness; D005260:Female; D016523:Foot Ulcer / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007564:Japan; D023821:Limb Salvage; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D013919:Thromboangiitis Obliterans / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D014945:Wound Healing; D055815:Young Adult
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor