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Gaffney, MM,Hynes, SO,Barry, F,O'Brien, T
2007
September
Cardiovascular gene therapy: current status and therapeutic potential
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1
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gene therapy cardiovascular disease therapeutic angiogenesis peripheral vascular disease coronary artery disease neointimal hyperplasia vein graft in-stent restenosis ENDOTHELIAL GROWTH-FACTOR HIND-LIMB ISCHEMIA CHRONIC MYOCARDIAL-ISCHEMIA PORCINE CORONARY-ARTERIES MESENCHYMAL STEM-CELLS INHIBITS NEOINTIMAL FORMATION ADENOVIRUS-MEDIATED TRANSFER DRUG-ELUTING STENTS DOUBLE-BLIND NITRIC-OXIDE
Gene therapy is emerging as a potential treatment option in patients suffering from a wide spectrum of cardiovascular diseases including coronary artery disease, peripheral vascular disease, vein graft failure and in-stent restenosis. Thus far preclinical studies have shown promise for a wide variety of genes, in particular the delivery of genes encoding growth factors such as vascular endothelial growth factor ( VEGF) and fibroblast growth factor ( FGF) to treat ischaemic vascular disease both peripherally and in coronary artery disease. VEGF as well as other genes such as TIMPs have been used to target the development of neointimal hyperplasia to successfully prevent vein graft failure and in-stent restenosis in animal models. Subsequent phase I trials to examine safety of these therapies have been successful with low levels of serious adverse effects, and albeit in the absence of a placebo group some suggestion of efficacy. Phase 2 studies, which have incorporated a placebo group, have not confirmed this early promise of efficacy. In the next generation of clinical gene therapy trials for cardiovascular disease, many parameters will need to be adjusted in the search for an effective therapy, including the identification of a suitable vector, appropriate gene or genes and an effective vector delivery system for a specific disease target. Here we review the current status of cardiovascular gene therapy and the potential for this approach to become a viable treatment option.
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DOI 10.1038/sj.bjp.0707315
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