Toxic neuropathy.

PURPOSE OF REVIEW

This paper examines recent research on toxic neuropathy and potential therapeutic developments. It also summarizes reports of new agents reported to cause peripheral neuropathy.

RECENT FINDINGS

Gene therapy with vasoactive endothelial growth factor, neurotrophic substances such as nerve growth factor and neurotrophin-3 are reported to reverse or protect against neurotoxicity in animal models. The neuroprotective effects of more established therapeutic agents like vitamin E, tacrolimus (FK 506) and erythropoietin hold promise for the immediate future. Cisplatin and high-dose pyridoxine are used more frequently to produce robust models of peripheral neuropathy in animals. Statins do appear to cause peripheral neuropathy. The incidence is low, however, and compared to its benefits in terms of cardiovascular protection, relatively innocuous. The profile of thalidomide neuropathy is becoming clearer as the indications for this drug increases. The incidence of thalidomide neuropathy is high, up to three quarters in some series, and although the information on dose dependency is variable, lower cumulative doses appear to be less toxic. Like thalidomide bortezomib, a novel proteosome inhibitor, is reportedly effective in the treatment of multiple myeloma and is associated with peripheral neuropathy. Oxaliplatin and epothilone are emerging anticancer drugs with neurotoxic potential. Similarly, leflunomide, a new disease modifying-agent approved for the treatment of rheumatoid arthritis, is reported to cause neuropathy.

SUMMARY

The study of toxic neuropathy is not only enhancing our knowledge of the mechanisms of neurotoxicity but also the neurobiology of peripheral neuropathy in general; and is likely to reveal avenues for therapeutics.