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

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.

Use of a constitutively active hypoxia-inducible factor-1alpha transgene as a therapeutic strategy in no-option critical limb ischemia patients: phase I dose-escalation experience.

Background: Critical limb ischemia, a manifestation of severe peripheral atherosclerosis and compromised lower-extremity blood flow, results in a high rate of limb loss. We hypothesized that adenoviral delivery of a constitutively active form of the transcription factor hypoxia-inducible factor-1alpha (ie, Ad2/HIF-1alpha/VP16 or HIF-1alpha) into the lower extremity of patients with critical limb ischemia would be safe and might result in a durable clinical response.

Methods And Results: This phase I dose-escalation program included 2 studies: a randomized, double-blind, placebo-controlled study and an open-label extension study.

Plasma vascular endothelial growth factor (VEGF) levels after intramuscular and intramyocardial gene transfer of VEGF-1 plasmid DNA.

The purpose of this study was to document the kinetics of vascular endothelial growth factor (VEGF) protein release into the systemic circulation after phVEGF gene transfer for therapeutic angiogenesis. VEGF plasma levels were measured by ELISA in 64 patients undergoing gene transfer of plasmid DNA: intramuscular in 34 patients with peripheral artery disease, and intramyocardial in 30 patients with coronary disease. Baseline plasma VEGF was highly variable and not normally distributed.

In vivo analysis of intramuscular gene transfer in human subjects studied by on-line ultrasound imaging.

The current study was designed to test the hypothesis that intramuscular (i.m.) injection of naked DNA leads to distribution of the injectate remote from the site of needle placement, a finding that might be expected to facilitate i.

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

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.