Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy

Ischemic peripheral neuropathy is a frequent, irreversible complication of lower extremity vascular insufficiency. We investigated whether ischemic pe ripheral neuropathy could be prevented and/or reversed by gene transfer of an endothelial cell mitogen designed to promote therapeutic angiogenesis. I ntramuscular gene transfer of naked DNA encoding vascular endothelial growt h factor (VEGF) simultaneously with induction of hindlimb ischemia in rabbi ts abrogated the substantial decrease in motor and sensory nerve parameters , and nerve function recovered promptly. When gene transfer was administere d 10 days after induction of ischemia, nerve function was restored earlier and/or recovered faster than in untreated rabbits. These findings are due i n part to enhanced hindlimb perfusion. In addition, however, the demonstrat ion of functional VEGF receptor expression by Schwann cells indicates a dir ect effect of VEGF on neural integrity as well. These findings thus constit ute a new paradigm for the treatment of ischemic peripheral neuropathy.