CLINICAL-EVIDENCE OF ANGIOGENESIS AFTER ARTERIAL GENE-TRANSFER OF PHVEGF(165) IN PATIENT WITH ISCHEMIC LIMB

Background Preclinical findings suggest that intra-arterial gene trans fer of a plasmid which encodes for vascular endothelial growth factor [VEGF) can improve blood supply to the ischaemic limb, We have used th e method in a patient. Methods Our patient was the eighth in a dose-ra nging series, She was aged 71 with an ischaemic right leg. We administ ered 2000 mu g human plasmid phVEGF(165) that was applied to the hydro gel polymer coating of an angioplasty balloon. By inflating the balloo n, plasmid DNA was transferred to the distal popliteal artery. Finding s Digital subtraction angiography 4 weeks after gene therapy showed an increase in collateral vessels at the knee, mid-tibial, and ankle lev els, which persisted at a 12-week view. Intra-arterial doppler-flow st udies showed increased resting and maximum flows (by 82% and 72%, resp ectively). Three spider angiomas developed on the right foot/ankle abo ut a week after gene transfer; one lesion was excised and revealed pro liferative endothelium, the other two regressed. The patient developed oedema in her right leg, which was treated successfully. Interpretati on Administration of endothelial cell mitogens promotes angiogenesis i n patients with limb ischaemia.