May 2002

Prospects for Vascular Endothelial Growth Factor Neurotherapeutics

Author Affiliations

Copyright 2002 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2002

Arch Neurol. 2002;59(5):692-694. doi:10.1001/archneur.59.5.692

VASCULAR ENDOTHELIAL growth factor (VEGF) plays an essential role in the growth of new blood vessels, contributes to the regulation of blood flow and vascular permeability, and has direct trophic effects on many cell types in addition to endothelium, including neurons and glia.15 Tissue hypoxia enhances local VEGF synthesis, leading to increased vascularity of the hypoxic tissue.2,6 Raising tissue VEGF levels by administration of recombinant VEGF or VEGF DNA also elicits neovascularization, and thus diminishes disability in animals with central nervous system (CNS) or peripheral nerve ischemia and in patients with coronary or limb arterial insufficiency. In experimental animals, VEGF therapy enhances recovery from focal brain ischemia and from neuropathy caused by ischemia or diabetes mellitus. Additional human VEGF trials can be anticipated in diabetic neuropathy and CNS ischemia. Genetically engineered ablation in mice of the transcriptional mechanism by which VEGF is induced by hypoxia causes motor neuron degeneration. This observation provides a rationale for future trials of VEGF in amyotrophic lateral sclerosis. Inhibitors of VEGF synthesis or signaling have shown promise in brain tumor therapy in experimental animals.

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