Comments for:

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Re: Can VEGF reverse diabetic neuropathy in human subjects?

Submitter: George L. King, M.D., and Aristidis Veves, M.D. | George.King@joslin.harvard.edu

Joslin Diabetes Center

Published July 6, 2001

To the Editor -- We agree with Dr. Crawford's comments regarding other possible techniques that can objectively measure changes in unmyelinated fibers in both experimental and human diabetes. However, we would like to point out that these techniques, although they have the potential to provide interesting results, are still in the development phase and have not been employed in large-scale studies. Moreover, these techniques are used in very few centers. Considerable work will be therefore required before any reasonable conclusions about their efficacy in testing new treatments can be reached. Until this is done, the behavioral tests will be probably the most widely employed and accepted tests.
Sincerely,
George L. King, M.D., and Aristidis Veves, M.D.

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Can VEGF reverse diabetic neuropathy in human subjects?

Submitter: Colin L. Crawford | clcraw13@hotmail.com

Department of Histopathology Imperial College of Medicine

Published June 28, 2001

Can VEGF reverse diabetic neuropathy in human subjects?
Colin L. Crawford
Department of Histopathology Imperial College of Medicine Charing Cross Hospital Fulham Palace Road London W6 8RF
e-mail clcraw13@hotmail.com Tel 07931 753 966
In their commentary (1), Veves and King state that, in experimental diabetic neuropathy ‘Changes in the unmyelinated fibers can be tested only indirectly by employing behavioral tests, such as the tailflick response to a thermal noxious stimulus’. It is however possible, at least in rabbits, to record both the amplitude and conduction velocity in C fibers, as demonstrated in an autoimmune peripheral nerve animal model (2). Unmyelinated fibre density can also be measured in the skin of the lower limbs using an antibody against Protein Gene Product (PGP) 9.5 (3).
As pain fiber loss is probably involved in the causation of trophic ulcers, characteristic bony changes in the metatarsals and Charcot’s joints in human diabetic neuropathy, the autoimmune animal model may also be more appropriate than those used by Schratzberger et al (4) for studying human diabetic neuropathy, as there was a decrease in amplitude in the faster component of C fibers after the animals were injected with a suspension of human peripheral nerve plus Freund’s Complete Adjuvant. The multiple treatments listed by Veves and King, which could be responsible for preventing nerve damage in diabetics could then be tested individually, or in combinations for their effect in reversing these changes in C fiber amplitude, before embarking on clinical trials in human subjects. Any changes in unmyelinated fibre density could also be recorded using an antibody to PGP after various treatments. .
1.Veves, A., and King, G.L. 2001. Can VEGF reverse diabetic neuropathy? J. Clin. Invest. 107: 1215-1218.
2. Crawford, C.L., and Hobbs, M.J. 1995. Neurotrophic factors in diabetic neuropathy. Trends Neurosci .18: 15-16.
3. McCarthy, B.G., Hsieh, S.-T., Stocks, M.A., Hauer, B.A., Macko, C., Cornblath, D.R., Griffin, J.W., and McCarthy, J.C. 1995. Cutaneous innervation in sensory neuropathies: Evaluation by skin biopsy. Neurology 45: 1848-1855.
4. Schratzberger, P., et al. 2001. Reversal of experimental diabetic neuropathy by VEGF gene expression. J.Clin.Invest. 107: 1083-1092.