Gene therapy in vascular disease

Background and purpose of the studyPeripheral artery disease is a highly prevalent disease which is characterised by high unmet medical need particularly in the more advanced stages of disease. Options comprise the need for vessel regeneration using therapeutic angiogenic gene therapy as well as the prevention of restenosis post-angioplasty using local gene therapy. Both problems have been addressed by extensive research. Recent advances in the knowledge of the complex regulation of angiogenesis and arteriogenesis and ways to its induction offer hope for a novel strategy that is based on the generation of such new vessels. This strategy termed “therapeutic angiogenesis” is a concept based on the use of angiogenic factors or stem cells or their combination to promote neovascularisation for the treatment of ischaemic tissues. This manuscript summarises the development of therapeutic angiogenic strategies using gene therapy.MethodsReview of current publications of phase I, II and III clinical trials and websites.Main findingsPhase II trials performed so far are difficult to compare due to different genes, vectors and applications routes used and different endpoints evaluated. Recently, the largest phase III trial did not confirm efficacy of non-viral gene transfer using the gene for fibroblast growth factor 1 in critical limb ischaemia.ConclusionsCardiovascular gene therapy, particularly, therapeutic angiogenesis has been shown to be safe, however, did not prove consistently efficacious in randomised controlled trials.