Gene therapy in the treatment of peripheral arterial disease

Br J Surg. 2012 Jan;99(1):6-15. doi: 10.1002/bjs.7743. Epub 2011 Nov 8.

Abstract

Background: Peripheral arterial disease remains a significant global health burden despite revolutionary improvements in endovascular techniques over the past decade. The durability of intervention for critical limb ischaemia is poor, and the condition is associated with high morbidity and mortality rates. To address this deficiency, alternative therapeutic options are being explored. Advances in the fields of gene therapy and therapeutic angiogenesis have led to these being advocated as potential future treatments.

Methods: Relevant medical literature from PubMed, Embase, the Cochrane Library and Google Scholar from the inception of these databases to June 2011 was reviewed.

Results: Encouraging outcomes in preclinical trials using a variety of proangiogenic growth factors have led to numerous efficacy and safety studies. However, no clinical study has shown significant benefit for gene therapy over placebo.

Conclusion: Identifying the optimal site for gene delivery, choice of vector and duration of treatment is needed if gene therapy is to become a credible therapeutic option for peripheral arterial disease.

Publication types

  • Review

MeSH terms

  • Calcium-Binding Proteins
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Adhesion Molecules
  • Controlled Clinical Trials as Topic
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / metabolism
  • Genetic Therapy* / methods
  • Genetic Vectors
  • Hepatocyte Growth Factor / genetics
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • Peripheral Arterial Disease / genetics*
  • Peripheral Arterial Disease / therapy*
  • Plasmids
  • Research Design
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Viruses

Substances

  • Calcium-Binding Proteins
  • Carrier Proteins
  • Cell Adhesion Molecules
  • EDIL3 protein, human
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factors
  • Hepatocyte Growth Factor