Improvement in chronic ischemic neuropathy after intramuscular phVEGF165 gene transfer in patients with critical limb ischemia

Arch Neurol. 2001 May;58(5):761-8. doi: 10.1001/archneur.58.5.761.


Objective: To investigate the effects of vascular endothelial growth factor gene therapy on ischemic neuropathy in patients with critical limb ischemia.

Design: An open-label, dose-escalating trial. Patients with angiographically proven critical leg ischemia received injections of phVEGF(165) human plasmid in the muscles of the ischemic limb. Testing before treatment and at 3 and 6 months included (1) symptom severity score, (2) clinical examination score, and (3) electrophysiologic studies. Clinical and electrophysiologic examiners were masked to each other's findings.

Setting: A tertiary care referral hospital and a major teaching affiliate of Tufts University School of Medicine, Boston, Mass.

Results: Of 29 consecutive patients enrolled, 17 (19 limbs) completed the 6 months of study. Six patients had diabetes. Compared with baseline studies, treated patients had significant clinical improvements in the symptom score (P<.01), sensory examination score (P<.01), total examination score (P =.01), peroneal motor amplitude (P =.03), and quantitative vibration threshold (P =.04). Improvement in the vascular ankle-brachial index in treated legs (P<.01) corresponded to improvement in neuropathy in the same limb. Neurologic improvement was seen in 4 of 6 patients with diabetes who completed the study. No clinical, electrophysiologic, or vascular improvements were observed in untreated legs.

Conclusions: Ischemic neuropathy might be a reversible condition, and therapeutic angiogenesis might be an effective treatment. The presence of diabetes does not preclude a response to this therapy.

MeSH terms

  • Adult
  • Aged
  • Chronic Disease
  • Cohort Studies
  • Critical Illness / therapy*
  • Electrophysiology
  • Endothelial Growth Factors / genetics*
  • Female
  • Gene Dosage
  • Gene Expression
  • Genetic Therapy*
  • Humans
  • Ischemia / physiopathology
  • Ischemia / therapy*
  • Leg / innervation*
  • Lymphokines / genetics*
  • Male
  • Middle Aged
  • Neovascularization, Physiologic
  • Peripheral Nerves / blood supply*
  • Peripheral Nerves / physiopathology
  • Prospective Studies
  • Sensation
  • Severity of Illness Index
  • Transgenes / genetics
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors