Therapeutic angiogenesis inhibits or rescues chemotherapy-induced peripheral neuropathy

Taxol- and thalidomide-induced injury of vasa nervorum is ameliorated by VEGF

Rudolf Kirchmair, Anne B. Tietz, Eleftheria Panagiotou, Dirk H. Walter, Marcy Silver, Youngsup Yoon, Peter Schratzberger, Alberto Weber, Kengo Kusano, David H. Weinberg, Allan H. Ropper, Jeffrey M. Isner, Douglas W. Losordo

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)69-75
Number of pages7
JournalMolecular Therapy
Volume15
Issue number1
DOIs
Publication statusPublished - 2007 Jan 1

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Vasa Nervorum
Thalidomide
Peripheral Nervous System Diseases
Paclitaxel
Vascular Endothelial Growth Factor A
Poisons
Drug Therapy
Wounds and Injuries
Therapeutics
Angiogenesis Inducing Agents
Electrophysiology
Peripheral Nerves
Genetic Therapy
Intercellular Signaling Peptides and Proteins
Plasmids
Animal Models
Cytokines
Injections
DNA
Incidence

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Kirchmair, Rudolf ; Tietz, Anne B. ; Panagiotou, Eleftheria ; Walter, Dirk H. ; Silver, Marcy ; Yoon, Youngsup ; Schratzberger, Peter ; Weber, Alberto ; Kusano, Kengo ; Weinberg, David H. ; Ropper, Allan H. ; Isner, Jeffrey M. ; Losordo, Douglas W. / Therapeutic angiogenesis inhibits or rescues chemotherapy-induced peripheral neuropathy : Taxol- and thalidomide-induced injury of vasa nervorum is ameliorated by VEGF. In: Molecular Therapy. 2007 ; Vol. 15, No. 1. pp. 69-75.
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abstract = "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.",
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Kirchmair, R, Tietz, AB, Panagiotou, E, Walter, DH, Silver, M, Yoon, Y, Schratzberger, P, Weber, A, Kusano, K, Weinberg, DH, Ropper, AH, Isner, JM & Losordo, DW 2007, 'Therapeutic angiogenesis inhibits or rescues chemotherapy-induced peripheral neuropathy: Taxol- and thalidomide-induced injury of vasa nervorum is ameliorated by VEGF', Molecular Therapy, vol. 15, no. 1, pp. 69-75. https://doi.org/10.1038/sj.mt.6300019

Therapeutic angiogenesis inhibits or rescues chemotherapy-induced peripheral neuropathy : Taxol- and thalidomide-induced injury of vasa nervorum is ameliorated by VEGF. / Kirchmair, Rudolf; Tietz, Anne B.; Panagiotou, Eleftheria; Walter, Dirk H.; Silver, Marcy; Yoon, Youngsup; Schratzberger, Peter; Weber, Alberto; Kusano, Kengo; Weinberg, David H.; Ropper, Allan H.; Isner, Jeffrey M.; Losordo, Douglas W.

In: Molecular Therapy, Vol. 15, No. 1, 01.01.2007, p. 69-75.

Research output: Contribution to journalArticle

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AB - 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.

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