Gene-based therapies in patients with critical limb ischemia

ABSTRACT

Introduction: Critical limb ischemia (CLI) constitutes a life-limiting and life-threatening disease. Revascularization, either endovascular or surgical, remains the best treatment option accompanied by medication and risk factor modification. Patients unable to undergo revascularization, referred as ‘no-option patients’, have been the center of interest the last few years, subjected to treatment therapies based on proteins (mainly growth factors) involved in angiogenesis via gene delivery to the ischemic tissue.

Areas covered: This review focuses on these growth factors, gives an update of the studies available, discusses the possible problems that influence outcomes and describes future perspectives including possible new technologies that will improve them. Additionally, the authors attempt to place therapeutic angiogenesis to the bigger frame of tailored therapy in CLI.

Expert opinion: Although encouraging in the beginning, growth factor therapy results have been equivocal and inconclusive. And while it would be misleading to approach gene therapy as panacea, its effect on the micro-circulatory level activating angiogenesis and arteriogenesis could act as an important adjunct in personalized treatment.

KEYWORDS:

• Angiogenesis
• critical limb ischemia
• Growth factor
• fibroblast growth factor
• hepatocyte growth factor
• vascular endothelial growth factor
• hypoxia inducible growth factor
• stromal derived growth factor
• gene therapy
• no-option CLI patients

Article highlights

• Gene therapy is currently reserved mainly for no-option CLI patients

• Results from RCTs investigating the role of gene therapy in angiogenesis for CLI patients are inconclusive

• HGF is the only growth factor so far to give promising results

• There is room for technical improvement in regard with drug delivery

• Gene therapy should be consider as an extra tool for CLI treatment with a view to tailored therapy approach

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This manuscript is not funded.