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Peripheral neuropathy discovery could lead to new drug therapies

Researchers have identified the underlying mechanisms of peripheral neuropathy (nerve damage), which could lead to new drug therapies.
Diabetes is linked to neuropathy, which can be caused by prolonged hyperglycemia. Neuropathy affects people with type 1 diabetes and type 2 diabetes and makes the feet particularly vulnerable, which is why it is important to maintain good quality of foot care and skin care.
A lack of understanding about peripheral neuropathy has restricted the developments of treatments for the condition, which can also be caused by chemotherapy, traumatic injury, heredity and other conditions.
In this new study, researchers at the MDI Biological Laboratory, Maine, United States used zebrafish larvae to model peripheral neuropathy. Because zebrafish larvae embryos develop rapidly and are translucent, they were ideal to study the progression of nerve degeneration in live animals.
The research team, led by Sandra Rieger, Ph.D, exposed zebrafish to paclitaxel, a chemotherapeutic agent used for treating ovaria, lung, breast and pancreatic cancers.
Paclitaxel induced the degeneration of sensory nerve endings by damaging the epidermis, which is supplied by free sensory nerve endings that establish direct contact with skin cells.
This degeneration was found to be caused by an increase in matrix-metalloproteinase 13 (MMP-13), an enzyme which degrades the collagen between the cells. Rieger’s team reported this increase in MMP-13 activity can be triggered by oxidative stress, which is also a sign of diabetic peripheral neuropathy.
When the zebrafish were treated with pharmological agents that reduce MMP-13 activity, the chemotherapy-induced nerve damage was reversed and the skin defects were improved.
Rieger added: “The general thinking is that no single drug can be effective for the treatment of all peripheral neuropathies, which stem from multiple causes. But our research indicates that there may potentially be a common underlying mechanism for some neuropathies affecting the sensory nervous system that could be manipulated with drugs targeting a single enzyme.”
Kevin Strange, Ph.D., president of the MDI Biological Laboratory, added: “[The] research has advanced [the] mission by elucidating a mechanism underlying peripheral neuropathy, opening the door to the development of therapeutic agents that can reverse nerve damage linked to chemotherapy, and possibly diabetes and other conditions.”
The researchers now plan to study the effect of MMP-13 on peripheral neuropathy in mammalian animals, while Mayo Clinic scientists are investigating the clinical relevance of these new findings in humans.
The findings appear in the Proceedings of the National Academy of Sciences.

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