Gene therapy as a novel therapeutic option in the treatment of peripheral vascular disease: systematic review and meta-analysis

Background: Stimulation of therapeutic angiogenesis using gene therapy is a novel intervention for peripheral vascular disease (PVD). Despite encouraging outcomes from animal studies and phase 1 trials, results from larger trials in this area have been conflicting. We undertook a systematic review and meta-analysis of randomised controlled trials in this field, to clarify the current situation. Methods: Medline, Embase, trial registries, the American Heart Association (AHA) abstract database and article reference lists were searched to identify randomised controlled trials of gene therapy for treatment of PVD. The outcomes were change in peak walking time and claudication onset time at 90 and 180 days post-treatment, and change in ankle-brachial pressure index (ABPI) at 90 days. Weighted mean differences (WMD) were calculated for these outcomes. Results: Five eligible randomised clinical trials were identified, containing 508 patients. There were no significant differences between control and intervention groups for any outcomes, irrespective of whether low-dose or high-dose gene therapy was tried. Conclusion: The available data suggests that gene therapy confers no benefit on patients with PVD. Closer examination of the individual trials shows that several have an excessive placebo response, which may go some way to explaining our result. Further research in this area in needed.