title: Double-blind, placebo-controlled study of HGF gene therapy in diabetic neuropathy.
abstract: OBJECTIVE
  To evaluate the safety and efficacy of a plasmid (VM202) containing two human hepatocyte growth factor isoforms given by intramuscular injections in patients with painful diabetic neuropathy.
  
  
  METHODS
  In a double-blind, placebo-controlled study, patients were randomized to receive injections of 8 or 16 mg VM202 per leg or placebo. Divided doses were administered on Day 0 and Day 14. The prospective primary outcome was change in the mean pain score measured by a 7 day pain diary. Secondary outcomes included a responder analysis, quality of life and pain measures, and intraepidermal nerve fiber density.
  
  
  RESULTS
  There were no significant adverse events attributable to VM202. Eighty-four patients completed the study. Patients receiving 8 mg VM202 per leg improved the most in all efficacy measures including a significant (P = 0.03) reduction at 3 months in the mean pain score and continued but not statistically significant reductions in pain at 6 and 9 months. Of these patients, 48.4% experienced a ≥50% reduction in pain compared to 17.6% of placebo patients. There were also significant improvements in the brief pain inventory for patients with diabetic peripheral neuropathy and the questionnaire portion of the Michigan Neuropathy Screening Instrument. Patients not on pregabalin or gabapentin had the largest reductions in pain.
  
  
  CONCLUSIONS
  VM202 was safe, well tolerated and effective indicating the feasibility of a nonviral gene therapy approach to painful diabetic neuropathy. Two days of treatment were sufficient to provide symptomatic relief with improvement in quality of life for 3 months. VM202 may be particularly beneficial for patients not taking gabapentin or pregabalin.
authors.affiliation: Northwestern University Chicago, Illinois.
authors.forename: John A
authors.initials: JA
authors.lastname: Kessler
authors.affiliation: University of Utah Salt Lake City, Utah.
authors.forename: A Gordon
authors.initials: AG
authors.lastname: Smith
authors.affiliation: Yonsei University College of Medicine Severence Hospital Seoul, South Korea.
authors.forename: Bong-Soo
authors.initials: BS
authors.lastname: Cha
authors.affiliation: Seoul National University Bundang Hospital Seoul, South Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Albany Medical Center Albany, New York.
authors.forename: James
authors.initials: J
authors.lastname: Wymer
authors.affiliation: Nerve and Muscle Center of Texas Houston, Texas.
authors.forename: Aziz
authors.initials: A
authors.lastname: Shaibani
authors.affiliation: Northwestern University Chicago, Illinois.
authors.forename: Senda
authors.initials: S
authors.lastname: Ajroud-Driss
authors.affiliation: Eastern Virginia Medical School Norfolk, Virginia.
authors.forename: Aaron
authors.initials: A
authors.lastname: Vinik