Angiogenesis and gene therapy in man - Dream or reality?

Preclinical studies indicate that angiogenic growth factors can stimulate t he development of collateral arteries in animal models of peripheral or myo cardial ischaemia, a concept termed 'therapeutic angiogenesis'. The goal of this review is to provide a brief overview of the advantages and disadvant ages of gene versus recombinant protein therapy for therapeutic angiogenesi s. We also discuss different options for delivering genes to patients, incl uding plasmids and modified viral vectors. Recently, the safety and potenti al utility of gene therapy for ischaemic disease were demonstrated in 3 cli nical trials involving the delivery of plasmid DNA encoding the 165 amino a cid isoform of human vascular endothelial growth factor (phVEGF(165)), a fa ctor that specifically promotes the proliferation and migration of vascular endothelial cells. Two trials involved the administration of phVEGF(165) f or peripheral arterial disease. In one trial, the plasmid was administered to the arterial wall from a hydrogel-coated angioplasty balloon, while a se cond trial examined the direct injection of phVEGF(165) into the skeletal m uscle of the affected limb. More recently, phVEGF(165) was directly injecte d into ischaemic myocardium. In all these trials, it appears that administr ation of phVEGF(165) led to improvements in tissue perfusion.