Gene therapy with VEGF

New therapeutic option: Atherosclerosis-related conditions are the primary cause of mortality in western countries. The incidence of severe limb-threa tening ischemia of the lower limbs reaches 500 to 1000 per million inhabita nts. The lack of effective treatment capable of preventing amputation in th e most severe cases has led to research into the development of collateral circulation to replace the occluded arteries. Preclinical data has demonstr ated that angiogenic factors can stimulate collateral circulation. This new therapeutic approach is called "angiogenesis therapy". VEGF: Vascular endothelial growth factor (VEGF) is a DNA fragment coding fo r a protein that has raised great expectations which are now entering the e ra of reality. Several administration routes are possible. The DNA fragment s can be deposited on the arterial wall using a catheter. The hydrogel ball on operates like an angioplasty ballon covered with a hydrophilic layer whi ch delivers the DNA fragments when inflated. More recently, the intramuscul ar route has been used to take advantage of the vascular distribution of th is angiogenic cytokine. The peripheral muscle cells can perform the transfo rmation via transcription to a messenger RNA for translation into the human DNA protein. A real application of gene therapy. Perspectives: Undeniable clinical benefit observed in the limited number of patients treated has led to proposing angiogenic cytokines for the treatme nt of ischemic heart disease when angioplasty or bypass surgery. The mob re cent series are small, but show that intramyocardial injection of VEGF is f easible. larger randomized series will evaluate these techniques. Despite t he large body of preclinical data, many questions remain unanswered. (C) 20 00, Masson, Paris.