• Sally A Price, Carolyn Dent, Beatriz Duran-Jimenez, Yuxin Liang, Lei Zhang, Edward J Rebar, Casey C Case, Philip D Gregory, Tyler J Martin, S Kaye Spratt, and David R Tomlinson.
• Faculty of Life Sciences, University of Manchester, Manchester, UK.
• Diabetes. 2006 Jun 1;55(6):1847-54.

AbstractPeripheral neuropathy is a common, irreversible complication of diabetes. We investigated whether gene transfer of an engineered zinc finger protein transcription factor (ZFP-TF) designed to upregulate expression of the endogenous vascular endothelial growth factor (VEGF)-A gene could protect against experimental diabetic neuropathy. ZFP-TF-driven activation of the endogenous gene results in expression of all of the VEGF-A isoforms, a fact that may be of significance for recapitulation of the proper biological responses stimulated by this potent neuroprotective growth factor. We show here that this engineered ZFP-TF activates VEGF-A in appropriate cells in culture and that the secreted VEGF-A protein induced by the ZFP protects neuroblastoma cell lines from a serum starvation insult in vitro. Importantly, single and repeat intramuscular injections of formulated plasmid DNA encoding the VEGF-A-activating ZFP-TF resulted in protection of both sensory and motor nerve conduction velocities in a streptozotocin-induced rat model of diabetes. These data suggest that VEGF-A-activating ZFP-TFs may ultimately be of clinical utility in the treatment of this disease.

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