title: Improvement in chronic ischemic neuropathy after intramuscular phVEGF165 gene transfer in patients with critical limb ischemia.
abstract: OBJECTIVE
  To investigate the effects of vascular endothelial growth factor gene therapy on ischemic neuropathy in patients with critical limb ischemia.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: St Elizabeth's Medical Center, 736 Cambridge St, Boston, MA 02135, USA.
authors.forename: D
authors.initials: D
authors.lastname: Simovic
authors.forename: J M
authors.initials: JM
authors.lastname: Isner
authors.forename: A H
authors.initials: AH
authors.lastname: Ropper
authors.forename: A
authors.initials: A
authors.lastname: Pieczek
authors.forename: D H
authors.initials: DH
authors.lastname: Weinberg
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D015331:Cohort Studies; D016638:Critical Illness / Q000628:therapy*; D004594:Electrophysiology; D016228:Endothelial Growth Factors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D015870:Gene Expression; D015316:Genetic Therapy; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D007866:Leg / Q000294:innervation*; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010525:Peripheral Nerves / Q000098:blood supply* / Q000503:physiopathology; D011446:Prospective Studies; D012677:Sensation; D012720:Severity of Illness Index; D019076:Transgenes / Q000235:genetics; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors