Vascular endothelial growth factor gene transfer for diabetic polyneuropathy: a randomized, double-blinded trial

Ann Neurol. 2009 Apr;65(4):386-93. doi: 10.1002/ana.21675.


Objective: Randomized, blinded trial of intramuscular gene transfer using plasmid vascular endothelial growth factor (VEGF) to treat diabetic polyneuropathy.

Methods: Diabetic patients with polyneuropathy were randomized to receive a VEGF-to-placebo ratio of 3:1. Three sets of injections were given at eight standardized sites adjacent to the sciatic, peroneal, and tibial nerves of one leg. Primary outcomes were change in symptom score at 6 months and a prespecified overall clinical and electrophysiological improvement score. Secondary outcomes were differences in symptoms, examination scores, visual analog pain scale, nerve conduction, and quantitative sensory testing.

Results: Thirty-nine patients received plasmid VEGF and 11 received placebo. Mean symptom score improved in both legs at 6 months, favoring VEGF over placebo (-1.2 +/- 0.5 vs -0.9 +/- 0.5; p < 0.01 after adjustment for change in the untreated leg) and compared with the untreated leg (-0.7 +/- 0.5; p = 0.02). The region of sensory loss and visual analog pain scale improved in the treated group (-1.5 vs -0.5; p = 0.01). Twelve of 39 VEGF versus 2 of 11 placebo patients met criterion for overall improvement. Other measures including nerve conduction potentials did not improve. There were 84 adverse events in VEGF patients, and 22 were serious; there were 51 events in placebo patients, and 2 were serious.

Interpretation: Intramuscular plasmid VEGF gene transfer improved diabetic neuropathic symptoms, meeting primary end-point criteria for efficacy but not affecting most secondary measures. Treatment was associated with more serious adverse events that did not reach statistical significance. These results are not conclusive but may justify further clinical study.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cohort Studies
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / therapy*
  • Double-Blind Method
  • Female
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Humans
  • Male
  • Middle Aged
  • Neural Conduction / genetics
  • Pain Measurement
  • Peripheral Nerves / physiopathology
  • Severity of Illness Index
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / genetics*
  • Vascular Endothelial Growth Factor A / therapeutic use*


  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A