Emerging drugs for diabetic neuropathy.
BACKGROUND
Diabetic neuropathy (DN) is a very common and disabling diabetes-related complication. DN is associated with significant morbidity and mortality. Diabetic peripheral neuropathy (DPN) can be painful in the earlier stages of the disease before becoming painless. Most of the currently available therapies are symptomatic (focusing on pain relief) rather than disease-modifying. With the exception of good glycemic control, there is currently no effective treatment to slow the progression of or reverse DPN.


METHODS
In this article, we review the epidemiology, pathogenesis, currently available and future treatments for DPN, and the potential development issues/challenges related to such new therapies. Literature search was performed using PubMed, Medline and Pharmaprojects from 1950 onwards. Search terms include a combination of terms such as diabetic neuropathy, pathogenesis, pathophysiology, mechanisms, treatment, therapy, oxidative/nitrosative stress, anti-oxidants, serotonin, nitrotyrosine, protein kinase C, aldose reductase, sodium channels, taurine, lipoic acid and poly (ADP-ribose) polymerase.


RESULTS
The reader will gain an overview of the epidemiology, clinical features and risk factors of DN. In addition, the reader will have a better understanding of the mechanisms that underpin the development of DPN and their relationships to the current and future therapies. The reader will also develop an insight into the limitations of the current approach to DPN treatment and the potential avenues for future research.


CONCLUSIONS
DN is a very common and disabling complication that currently has no effective treatments other than diabetes control. The pathogenesis of DPN is complex and multi-factorial. Several disease-modifying and symptomatic treatments are currently under development. Oxidative and nitrosative stress have been identified as key pathogenic factors in the development of DPN and new treatments target these pathways and/or their downstream consequences. Gene therapy and growth factors have also emerged as potential new therapies that target particular cellular compartments as opposed to being delivered systemically. The recognition of the difficulty in reversing established DN has focused efforts on slowing its progression.
Tahrani
Abd A
AA
University of Birmingham, Centre of Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, Birmingham, UK.
Askwith
Trevor
T
Stevens
Martin J
MJ
D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy; D016503:Drug Delivery Systems; D015195:Drug Design; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D018384:Oxidative Stress; D012307:Risk Factors