Summing up
The combination of an understanding of a widening range of underlying diseases, advancements in cancer therapies, and the rising prevalence of diabetes have all led to an increasing incidence of peripheral neuropathy. Coupled with the fact that one-third of patients with peripheral neuropathy experience idiopathic neuropathy, this indicates that extensive studies must be undertaken to identify mitigation and prevention strategies for peripheral neuropathy. To summarize the landscape of treatment for peripheral neuropathy:
Diabetic peripheral neuropathy. Treatment for DPN comprises three FDA-approved products: pregabalin, duloxetine, and a higher (8%)-strength capsaicin patch.3 Pain-management therapies also exist to reduce diabetes-induced neuropathic pain, including gabapentin, amitriptyline, and extended-release tapentadol.10
Chemotherapy-induced peripheral neuropathy has yet to be effectively treated in humans; however, many trials are being completed in animals with promising results. Treatment for CIPN has been identified using senolytic agents, such as navitoclax,22 and through inhibition of SASP by a variety of agents, including ARV825, tocilizumab, and adalimumab.23-26
Oxaliplatin-induced peripheral neuropathy. Research has identified a potential preventive agent in duloxetine, with human trials already showing efficacy and safety.29 Animal models have shown progress studying antioxidant agents, such as amifostine31 and calmangafodipir,32 which target ion channels. In a similar mechanism of action, riluzole has been observed to reduce motor and sensory deficits and depression resulting from treatment with oxaliplatin.
Vincristine-induced peripheral neuropathy. Progress has been seen in treating vincristine-induced peripheral neuropathy with pyridoxine and pyridostigmine, which have improved neuropathy scores in trial subjects;37 more studies must be completed before these agents can be established as effective therapy.
Autoimmune PN. There are no FDA-approved drugs to mitigate the peripheral neuropathy induced by GBS and CIDP; however, studies are being conducted to resolve this impediment. Potential treatments, such as ANX005, a recombinant antibody, and eculizumab, a monoclonal antibody, have both shown efficacy in human trials and provide a potential path toward treatment against peripheral neuropathy caused by GBS.47,50 CIDP is currently treated using prednisone, plasmapheresis, and IVIG.40 Clinical trials are studying the efficacy of rituximab and efgartigimod for CIDP.58-60
Infection-induced peripheral neuropathy. Although many infections can induce peripheral neuropathy, HIV is most well documented and therefore was singled out for discussion in this article. Pirenzepine has been shown to promote neurite growth and reduce mitochondrial degeneration – both of which factors are associated with reduction of neuropathic pain.66 Exercise and analgesics have also been found to mitigate the effects of HIV-induced distal sensory neuropathy, with pain scores being reduced.61
Cryptogenic sensory polyneuropathy. Research has yet to identify a causative agent of, or subsequent potential therapy for, CSPN. Increased knowledge about this neuropathy will, it is hoped, bring patients closer to a cure – beyond current pain mitigation strategies with anticonvulsants, antidepressants, and opioid-like compounds.3
Ms. Lee is a first-year master of science candidate in applied life sciences, with an emphasis on infectious diseases, and Mr. Kosacki is a first-year master of science candidate in applied life sciences, with an emphasis on translational research, both at Keck Graduate Institute Henry E. Riggs School of Applied Life Sciences, Claremont, Calif. Dr. Bhandari is professor of clinical sciences and Dr. Tran is professor of clinical sciences, Keck Graduate Institute School of Pharmacy and Health Sciences.