Gene therapy for cardiovascular angiogenesis

Abstract

Atherosclerosis and endothelial dysfunction are responsible for the pathophysiologic basis of the spectrum of cardiovascular disorders including ischaemic heart disease (IHD), the leading cause of morbidity and mortality in the US. There have been major advances, including the use of pharmacotherapy, coronary and peripheral percutaneous transluminal interventions (PTI), coronary and peripheral bypass surgery and primary/secondary prevention measures. There are, however, multiple unmet needs: IHD refractory to medical therapy and unsuitable for revascularisation; critical limb ischaemia unsuitable for PTI or surgery; restenosis; ischaemic/diabetic neuropathy and heart failure. Cardiovascular gene therapy (GT) with vascular endothelial growth factor (VEGF) has yielded improved perfusion and reduced ischaemia in preclinical models of IHD. Several preclinical studies and Phase I and II clinical trials have shown the safety and therapeutic potential of GT in the treatment of IHD, peripheral arterial disease (PAD), restenosis, and ischaemic and diabetic neuropathy, pointing to the need for Phase III clinical trials.