Therapeutic angiogenesis inhibits or rescues chemotherapy-induced peripheral neuropathy: taxol- and thalidomide-induced injury of vasa nervorum is ameliorated by VEGF

Mol Ther. 2007 Jan;15(1):69-75. doi: 10.1038/


Toxic neuropathy represents an important clinical problem in the use of the chemotherapeutic substances Taxol and thalidomide. Sensory neuropathy has a high incidence, lacks an effective treatment and is the dose-limiting factor for these drugs. The pathogenic basis of these neuropathies is unknown. We investigated the hypothesis that the experimental toxic neuropathies from Taxol and thalidomide results from destruction of vasa nervorum and can be reversed by the administration of an angiogenic cytokine. In animal models of Taxol- and thalidomide-induced neuropathy, nerve blood flow has been attenuated and the number of vasa nervorum has been reduced. Intramuscular gene transfer of naked plasmid DNA encoding VEGF-1 administered in parallel with Taxol injections completely inhibited deterioration of nerve function and diminution of the peripheral nerve vasculature. Gene therapy in animals with established Taxol- or thalidomide-induced neuropathies resulted in recovery of vascularity and improved nerve electrophysiology. These findings implicate microvascular damage as the basis for toxic neuropathy and suggest that angiogenic growth factors may constitute a novel treatment for this disorder.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cells, Cultured
  • Drug Therapy, Combination
  • Electrophysiology
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology
  • Humans
  • Injections, Intramuscular
  • Lectins / pharmacology
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mitogen-Activated Protein Kinases / metabolism
  • Neovascularization, Pathologic / drug therapy*
  • Paclitaxel / pharmacology*
  • Peripheral Nervous System Diseases / chemically induced*
  • Peripheral Nervous System Diseases / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plasmids / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation
  • Thalidomide / pharmacology*
  • Vasa Nervorum / drug effects*
  • Vasa Nervorum / injuries*
  • Vascular Endothelial Growth Factor A / pharmacology*


  • Lectins
  • Vascular Endothelial Growth Factor A
  • Thalidomide
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Paclitaxel