title: Clinical Safety and Preliminary Efficacy of Plasmid pUDK-HGF Expressing Human Hepatocyte Growth Factor (HGF) in Patients with Critical Limb Ischemia.
abstract: OBJECTIVE
  Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease and a major unmet public health care need. This phase I clinical study was performed to assess the safety and preliminary efficacy of naked plasmid DNA (pUDK-HGF) expressing human hepatocyte growth factor (HGF) in patients with critical limb ischemia (CLI).
  
  
  METHODS
  Twenty-one patients with CLI were enrolled and randomly divided into four dose groups (4-16 mg) to receive local injection of pUDK-HGF into ischemic calf and/or thigh muscles twice on days 1 and 15. Safety, including adverse events and physiological parameters, and preliminary efficacy, including pain severity score (VAS), ulcer size, transcutaneous oxygen pressure (TcPO2), and ankle brachial index (ABI), were evaluated throughout a 3 month follow up period.
  
  
  RESULTS
  All doses of pUDK-HGF were well tolerated by the patients. None of the adverse effects was considered to be related to pUDK-HGF injection. Two significant clinical results were observed after pUDK-HGF administration. The mean VAS value of all patients decreased from 4.52 at baseline to 0.30 (p < .01), and pain had disappeared in 14 out of 17 evaluable patients by day 91. Two of four ulcers had completely healed, with the other two patients having more than 25% ulcer size reduction in the long axis diameter. Of five patients with gangrene, one gangrenous wound had healed completely and two patients showed marked size reduction by day 91. The mean hemodynamic parameters (ABI, TcPO2) were also improved.
  
  
  CONCLUSIONS
  Intramuscular injection of pUDK-HGF is safe, and may provide symptomatic relief for CLI patients. A larger, randomized, double blinded phase II trial will provide more information on safety and efficacy.
authors.affiliation: Vascular Surgery Department of Xuan Wu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Cui
authors.affiliation: Vascular Surgery Department of Xuan Wu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.affiliation: Vascular Surgery Department of Xuan Wu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Vascular Surgery Department of Xuan Wu Hospital, Institute of Vascular Surgery, Capital Medical University, Beijing, China. Electronic address: guyongquan1234@163.com.
authors.forename: Y
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Fu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Dong
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Song
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Hu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Humanwell Healthcare Group Co., Ltd., Wuhan, China.
authors.forename: D
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing, China. Electronic address: qinglz@yahoo.com.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D055109:Ankle Brachial Index; D001785:Blood Gas Monitoring, Transcutaneous; D002681:China; D016638:Critical Illness; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006439:Hemodynamics; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007273:Injections, Intramuscular; D007383:Intermittent Claudication / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D007511:Ischemia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D007871:Leg Ulcer / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D011446:Prospective Studies; D020127:Recovery of Function; D013997:Time Factors; D016896:Treatment Outcome; D014945:Wound Healing; D055815:Young Adult
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor
keywords: Critical limb ischemia; Hepatocyte growth factor; Naked DNA