Contemporary view on the treatment of lower limb peripheral arterial diseases: the role of genetic engineering

ABSTRACT

Peripheral arterial disease (PAD) remains a growing global health problem. Its prevalence is increasing worldwide, affecting more than 200 million people. Treatment of moderate disease includes risk factor elimination, exercise, antithrombotic agents, and Cilostazol or possibly Pentoxifylline depending on symptoms. Severe lower limb PAD usually requires endovascular correction (angioplasty) or bypass surgery and may lead to amputation; mortality is high. The prognosis, in general, with treatment, is not fully satisfactory for specialists. Gene therapy offers the opportunity to modify the clinical course of PAD using strategies that increase vascular supply through angiogenesis and arteriogenesis, improving muscle perfusion and function in ischemic lower limbs. This paper discusses gene therapy approaches in the context of PAD, both intermittent claudication and critical limb ischemia, and the prospects for adeno-associated virus-based strategies delivering not only vascular endothelial growth factor but also a range of other mediators as potential new therapeutic agents.