Nerve growth factor prevents experimental cisplatin neuropathy.
Cisplatin is a widely used antitumor agent, the dose-limiting toxicity of which is predominantly large-fiber sensory neuropathy. Prevention of such a neuropathy would extend the usefulness of this agent, allowing higher doses and longer periods of treatment. We report here that we have successfully established cisplatin neuropathy in mice measured by using behavioral, biochemical, and electrophysiological techniques, and that subcutaneous administration of human recombinant nerve growth factor (NGF) prevents or delays the neuropathy. Cisplatin administration reduced sensory ganglion levels of the peptide transmitter, calcitonin gene-related peptide, slowed nerve conduction in the tail and impaired proprioception as measured by the ability to balance on a rotating dowel. NGF coadministration appeared to prevent all these abnormalities. Treatment of the human toxic neuropathy with its well-established time of onset, simple clinical course, and the accessibility of nerve to NGF administered systemically may provide the best clinical setting for the first human trials of NGF.
Apfel
S C
SC
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461.
Arezzo
J C
JC
Lipson
L
L
Kessler
J A
JA
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D005727:Ganglia, Spinal / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000032:analysis; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control; D009431:Neural Conduction / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011434:Proprioception / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012677:Sensation; D012684:Sensory Thresholds / Q000187:drug effects
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D015740:Calcitonin Gene-Related Peptide; D002945:Cisplatin