Scientist identifies mechanism underlying peripheral neuropathy

April 14, 2016, Mount Desert Island Biological Laboratory
Recent research by Sandra Rieger, Ph.D., of the MDI Biological Laboratory identifying the underlying mechanisms of peripheral neuropathy, or nerve damage, has raised the prospect that drug therapies can be developed for the treatment of this condition, which causes pain, numbness and/or tingling in the hands and feet. The research was published March 28 in the Proceedings of the National Academy of Sciences. Credit: MDI Biological Laboratory

Recent research by Sandra Rieger, Ph.D., of the MDI Biological Laboratory identifying the underlying mechanisms of peripheral neuropathy, or nerve damage, has raised the prospect that drug therapies can be developed for the treatment of this condition, which causes pain, numbness and/or tingling in the hands and feet. The research was published March 28 in the Proceedings of the National Academy of Sciences.

Peripheral nerve damage is a common condition affecting nearly 8 million people in the United States, but until now a lack of understanding of the underlying mechanisms has held back the development of treatments. Drugs exist for the treatment of symptoms - pain relievers, for instance - but not for the condition itself, which can be caused by chemotherapy, diabetes, traumatic injury, heredity and other conditions.

"Our goal is to develop treatments that activate the repair and regeneration of damaged tissues," said Kevin Strange, Ph.D., president of the MDI Biological Laboratory. "Sandra Rieger's research has advanced that 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 MDI Biological Laboratory, located in Bar Harbor, Maine, is an independent, nonprofit biomedical research institution focused on increasing healthy lifespan and harnessing our natural ability to repair and regenerate tissues damaged by injury or disease. The institution develops solutions to human health problems through research, education and ventures that transform discoveries into cures.

Rieger and other scientists working in the institution's Kathryn W. Davis Center for Regenerative Medicine study tissue repair, regeneration and aging in a diverse range of organisms that have robust mechanisms to repair and regenerate lost and damaged tissues.

"The general thinking is that no single drug can be effective for the treatment of all peripheral neuropathies, which stem from multiple causes," Rieger said. "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."

Rieger conducted her research in zebrafish exposed to paclitaxel, a chemotherapeutic agent used for ovarian, breast, lung, pancreatic and other cancers. Paclitaxel-induced peripheral neuropathy affects the majority of treated patients; however, those who are most severely affected (about 30 percent) have to terminate chemotherapy or reduce the dose because of this condition, which can impact cancer survival.

Rieger used zebrafish larvae to model peripheral neuropathy because the embryos develop rapidly and because the larval fish are translucent, making them ideal for studying the progression of nerve degeneration in live animals.

Rieger's research showed that paclitaxel induces the degeneration of sensory nerve endings by damaging the outer layer of the skin, or epidermis. The epidermis is innervated by free that establish direct contact with skin cells. Her research showed that degeneration is caused by perturbations in the epidermis due to an increase in matrix-metalloproteinase 13 (MMP-13), an enzyme that degrades the collagen, or "glue," between the cells. The increase in MMP-13 activity could be triggered by oxidative stress, which is also a hallmark of .

In the research, Rieger treated the zebrafish with pharmacological agents that reduce MMP-13 activity, with the result that skin defects were improved and chemotherapy-induced was reversed. The treatment of neuropathy with MMP-13- targeting compounds is the subject of a provisional patent filed by the MDI Biological Laboratory in January.

MMP-13 over-activation has also been linked to various other disease conditions, such as tendon injury, intestinal inflammatory and cancer, raising the possibility that drugs developed to treat peripheral neuropathy could yield other health benefits as well.

The next step is to study the effect of MMP-13 on in mammalian models. Studies are also underway in collaboration with the Mayo Clinic in Rochester, Minn., to test the clinical relevance of these findings in humans.

Explore further: Potential new drug therapy for peripheral nerve damage announced

More information: Thomas S. Lisse et al. Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish, Proceedings of the National Academy of Sciences (2016). DOI: 10.1073/pnas.1525096113

Related Stories

Potential new drug therapy for peripheral nerve damage announced

February 22, 2016
The Mount Desert Island (MDI) Biological Laboratory has announced that assistant professor Sandra Rieger, Ph.D., has identified two drugs that could potentially be used to reverse peripheral nerve damage, or peripheral neuropathy, ...

Study provides new understanding of diabetic peripheral neuropathy

April 11, 2016
A research team from Wayne State University recently published a paper in the Journal of Clinical Investigation that provides a paradigm shift in the understanding of cellular and molecular mechanisms underlying diabetic ...

Scientist identifies mechanism to regenerate heart tissue

March 9, 2016
The MDI Biological Laboratory has announced new discoveries about the mechanisms underlying the regeneration of heart tissue by Assistant Professor Voot P. Yin, Ph.D., which raise hope that drugs can be identified to help ...

YouTube videos on peripheral nerve pain may misguide patients

October 21, 2015
Researchers who combed YouTube for videos regarding peripheral neuropathy, or nerve damage that causes weakness, numbness, and pain in the hands and feet, found 200 videos, but only about half of them were from healthcare ...

Small nerve fibers defy neuropathy conventions

April 11, 2016
Results of a small study of people with tingling pain in their hands and feet have added to evidence that so-called prediabetes is more damaging to motor nerves than once believed, in a report on the study published online ...

Nerve damage from chemo may affect cancer survivors for years

January 15, 2016
(HealthDay)—Many women who survive cancer have symptoms of chemotherapy-related nerve damage in their feet and hands years after treatment, a new study reveals.

Recommended for you

Research shows signalling mechanism in the brain shapes social aggression

October 19, 2018
Duke-NUS researchers have discovered that a growth factor protein, called brain-derived neurotrophic factor (BDNF), and its receptor, tropomyosin receptor kinase B (TrkB) affects social dominance in mice. The research has ...

Good spatial memory? You're likely to be good at identifying smells too

October 19, 2018
People who have better spatial memory are also better at identifying odors, according to a study published this week in Nature Communications. The study builds on a recent theory that the main reason that a sense of smell ...

How clutch molecules enable neuron migration

October 19, 2018
The brain can discriminate over 1 trillion odors. Once entering the nose, odor-related molecules activate olfactory neurons. Neuron signals first accumulate at the olfactory bulb before being passed on to activate the appropriate ...

Scientists discover the region of the brain that registers excitement over a preferred food option

October 19, 2018
At holiday buffets and potlucks, people make quick calculations about which dishes to try and how much to take of each. Johns Hopkins University neuroscientists have found a brain region that appears to be strongly connected ...

Gene plays critical role in noise-induced deafness

October 19, 2018
In experiments using mice, a team of UC San Francisco researchers has discovered a gene that plays an essential role in noise-induced deafness. Remarkably, by administering an experimental chemical—identified in a separate ...

Weight loss success linked with active self-control regions of the brain

October 18, 2018
New research suggests that higher-level brain functions have a major role in losing weight. In a study among 24 participants at a weight-loss clinic, those who achieved greatest success in terms of weight loss demonstrated ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.