Gene therapy trial in peripheral vascular disease
Early indications are that gene therapy can help in the treatment of patients with peripheral vascular disease, said Professor Seppo Ylä-Herttuala (University of Kuopio, Finland).
He reported interim results from a trial involving patients with severe lower limb ischaemia who were given arterial gene therapy during angioplasty.
The trial included 27 patients: nine in a control group (angioplasty only) and 18 who received therapy with the gene for vascular endothelial growth factor (VEGF), delivered either via liposomes or adenoviruses. Treadmill tests to assess improvement had not yet been carried out. However, angiographic studies had shown definite increased vascularity in the treated legs.
Professor Ylä-Herttuala said that it was unclear whether the improved vascularity resulted from production of new blood vessels or improved flow through previously blocked vessels. As well as inducing new vessels (angiogenesis), VEGF was vasculoprotective. It stimulated endothelial production of nitric oxide and prostacyclin, which had vasodilator and antiplatelet properties. The process of opening up an atherosclerotic artery by angioplasty could itself damage the endothelium (the inner lining of the blood vessel), and this, in turn, frequently led to restenosis and thrombosis. VEGF might stimulate endothelial repair and prevent platelet aggregation.
In the trial, benefit was maintained at three-month follow up, although the gene would only be expected to be expressed for two to three weeks. Professor Ylä-Herttuala suggested that VEGF helped with the initial re-establishing of blood flow and then “nature keeps the vessel open.” If this type of treatment turned out to be successful, repeat gene therapy might be needed every six months or so. He emphasised that the gene therapy only had a local effect, so minimising any concern over stimulation of angiogenesis in tumours.
VEGF could not be injected directly because it was cleared very rapidly (within two minutes). The gene therapy appeared to be safe, although some patients receiving the adenoviral vector (which was more effective than liposome transfer) had fever and slight increases in liver enzymes. Professor Ylä-Herttuala emphasised that randomised trials, with controls, were essential in gene therapy. Trials had not always been carried out properly and this had led to the recent negative publicity about this type of therapy.
Citation: The Pharmaceutical Journal URI: 20002124
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