New treatment strategy for patients with CMT disease on the horizon

Published on April 29, 2013 at 4:25 AM · 2 Comments

Neuroscientists at UB's Hunter James Kelly Research Institute show how turning down synthesis of a protein improves nerve, muscle function in common neuropathy

A potential new treatment strategy for patients with Charcot-Marie-Tooth disease is on the horizon, thanks to research by neuroscientists now at the University at Buffalo's Hunter James Kelly Research Institute and their colleagues in Italy and England.

The institute is the research arm of the Hunter's Hope Foundation, established in 1997 by Jim Kelly, Buffalo Bills Hall of Fame quarterback, and his wife, Jill, after their infant son Hunter was diagnosed with Krabbe Leukodystrophy, an inherited fatal disorder of the nervous system. Hunter died in 2005 at the age of eight. The institute conducts research on myelin and its related diseases with the goal of developing new ways of understanding and treating conditions such as Krabbe disease and other leukodystrophies.

Charcot-Marie-Tooth or CMT disease, which affects the peripheral nerves, is among the most common of hereditary neurological disorders; it is a disease of myelin and it results from misfolded proteins in cells that produce myelin.

The new findings, published online earlier this month in The Journal of Experimental Medicine, may have relevance for other diseases that result from misfolded proteins, including Alzheimer's disease, Parkinson's, multiple sclerosis, Type 1 diabetes, cancer and mad cow disease.

A graphic and a picture of the researcher are available at http://www.buffalo.edu/news/releases/2013/04/056.html.

The paper shows that missteps in translational homeostasis, the process of regulating new protein production so that cells maintain a precise balance between lipids and proteins, may be how some genetic mutations in CMT cause neuropathy.

CMT neuropathies are common, hereditary and progressive; in severe cases, patients end up in wheelchairs. These diseases significantly affect quality of life but not longevity, taking a major toll on patients, families and society, the researchers note.

"It's possible that our finding could lead to the development of an effective treatment not just for CMT neuropathies but also for other diseases related to misfolded proteins," says Lawrence Wrabetz, MD, director of the institute and professor of neurology and biochemistry in UB's School of Medicine and Biomedical Sciences and senior author on the paper. Maurizio D'Antonio, of the Division of Genetics and Cell Biology of the San Raffaele Scientific Institute in Milan is first author; Wrabetz did most of this research while he was at San Raffaele, prior to coming to UB.

The research finding centers around the synthesis of misfolded proteins in Schwann cells, which make myelin in nerves. Myelin is the crucial fatty material that wraps the axons of neurons and allows them to signal effectively. Many CMT neuropathies are associated with mutations in a gene known as P0, which glues the wraps of myelin together. Wrabetz has previously shown in experiments with transgenic mice that those mutations cause the myelin to break down, which in turn, causes degeneration of peripheral nerves and wasting of muscles.

When cells recognize that the misfolded proteins are being synthesized, cells respond by severely reducing protein production in an effort to correct the problem, Wrabetz explains. The cells commence protein synthesis again when a protein called Gadd34 gets involved.

"After cells have reacted to, and corrected, misfolding of proteins, the job of Gadd34 is to turn protein synthesis back on," says Wrabetz. "What we have shown is that once Gadd34 is turned back on, it activates synthesis of proteins at a level that's too high-that's what causes more problems in myelination.

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Comments
  1. Mónica Núnez Mónica Núnez Spain says:

    Hello!

    I am a woman who has CMT disease so I would like to know when will the first treatment.

    Thank you very much.

    Regards.

  2. maria zein maria zein United States says:

    hello there!
    I am 22 years old girl with CMT, I was wondering to know how I can start the treatment and is it possible to send my Documents?
    thank you

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