Blocking neuron signaling pathway could lead to new treatments for peripheral neuropathy

January 17, 2017, University of California - San Diego
A colorized electron micrograph depicting mitochondria. These organelles -- the power plants of every cell -- play a critical role in peripheral nerve growth regeneration. Credit: Thomas Deerinck, National Center for Microscopy and Imaging Research, UC San Diego.

Researchers at University of California San Diego School of Medicine, with colleagues at the National Institute of Diabetes and Digestive and Kidney Diseases, the University of Manitoba and St. Boniface Hospital Albrechtsen Research Centre in Canada, have identified a molecular signaling pathway that, when blocked, promotes sensory neuron growth and prevents or reverses peripheral neuropathy in cell and rodent models of type 1 and 2 diabetes, chemotherapy-induced neuropathy and HIV.

The findings are published in the January 17, 2017 issue of the Journal of Clinical Investigation.

Peripheral neuropathy (PR) is a condition resulting from damage to the peripheral nervous system—the vast communications network that transmits information between the central nervous system (brain and spinal cord) and the rest of the body. Symptoms range from numbness, tingling and muscle weakness to severe pain, paralysis and organ dysfunction. An estimated 20 million Americans have some form of PR, which can be a symptom of many diseases, including diabetes and HIV, or a side effect of some chemotherapies.

"Peripheral neuropathy is a major and largely untreated cause of human suffering," said first author Nigel Calcutt, PhD, professor of pathology at UC San Diego School of Medicine. "It has huge associated health care costs."

Previous research has described at least some of the fundamental processes involved in healthy, on-going peripheral nerve growth regeneration, including the critical role of mitochondria—cellular organelles that produce adenosine triphosphate (ATP), the energy-carrying molecule found in all cells that is vital to driving nerve recovery after injury.

In their JCI paper, the researchers looked for key molecules and mechanisms used in sensory and regrowth. In particular, they noted that the outgrowth of neurites—projections from a neuronal cell body that connect it to other neurons—was constrained by activation of muscarinic acetylcholine receptors. This was surprising, they said, because acetylocholine is a neurotransmitter usually associated with activation of cells.

With identification of this signaling pathway, the scientists suggest it is now possible to investigate the utility of anti-muscarinic drugs already approved for use in other conditions as a new treatment for .

"This is encouraging because the safety profile of anti-muscarinic drugs is well-characterized, with more than 20 years of clinical application for a variety of indications in Europe," said senior study author Paul Fernyhough, PhD, professor in the departments of pharmacology and therapeutics and physiology at the University of Manitoba in Canada. "The novel therapeutic application of anti-muscarinic antagonists suggested by our studies could potentially translate relatively rapidly to clinical use."

Explore further: A potential target for peripheral neuropathy treatment discovered

More information: Nigel A. Calcutt et al, Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy, Journal of Clinical Investigation (2003). DOI: 10.1172/JCI15792

Related Stories

A potential target for peripheral neuropathy treatment discovered

August 3, 2016
Whole exome sequencing has revealed a novel mechanism and potential target for treating peripheral neuropathy, a condition that afflicts millions of people in the United States alone.

Genetic biomarker may predict nerve pain side effects associated with prostate cancer treatment

May 13, 2016
Taxanes are a group of drugs commonly used to treat cancers of the breast, lung, ovary, or prostate, but its use can be limited by significant side effects. Researchers from Moffitt Cancer Center report prostate cancer patients ...

Scientist identifies mechanism underlying peripheral neuropathy

April 14, 2016
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 ...

Brain tumours and peripheral neuropathy

March 5, 2013
(Medical Xpress)—Researchers from Plymouth University Peninsula Schools of Medicine and Dentistry are part of an international team which has for the first time identified the role of a tumour suppressor in 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 ...

Recommended for you

Therapeutic antibodies protected nerve–muscle connections in a mouse model of Lou Gehrig's disease

February 20, 2018
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, causes lethal respiratory paralysis within several years of diagnosis. There are no effective treatments to slow or halt this devastating disease. Mouse ...

Brain liquefaction after stroke is toxic to surviving brain: study

February 20, 2018
Scientists have known for years that the brain liquefies after a stroke. If cut off from blood and oxygen for a long enough period, a portion of the brain will die, slowly morphing from a hard, rubbery substance into liquid ...

Brain immune system is key to recovery from motor neuron degeneration

February 20, 2018
The selective demise of motor neurons is the hallmark of Lou Gehrig's disease, also known as amyotrophic lateral sclerosis (ALS). Yet neurologists have suspected there are other types of brain cells involved in the progression ...

Brain aging may begin earlier than expected

February 20, 2018
Physicists have devised a new method of investigating brain function, opening a new frontier in the diagnoses of neurodegenerative and ageing related diseases.

Every experience that the brain perceives is unique

February 20, 2018
Neuronal activity in the prefrontal cortex represents every experience as "novel." The neurons adapt their activity accordingly, even if the new experience is very similar to a previous one. That is the main finding of a ...

Electrical implant reduces 'invisible' symptoms of man's spinal cord injury

February 19, 2018
An experimental treatment that sends electrical currents through the spinal cord has improved "invisible" yet debilitating side effects for a B.C. man with a spinal cord injury.

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.