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ARTICLE: New Method Found To Slow Nerve Disease
Associated Press

WASHINGTON — A new method of slowing the most common inherited nerve disease may point the way for novel treatments for
nerve disorders.

Researchers working with rats retarded the progression of CMT, which gradually reduces the ability to use the arms and
legs and affects about one in 2,500 Americans. The team found success using a chemical that blocks a protein associated
with more than half of all cases of CMT. People with the most common form of CMT have a genetic defect that causes
overproduction of that protein.

While the chemical, onapristone, probably would not be useful in humans with CMT because of the side effects, other
drugs in the same class may work and cause fewer problems, said an expert not involved in the study.

CMT stands for Charcot-Marie-Tooth disease, named for the doctors who identified it in 1886, Jean-Marie Charcot, Pierre
Marie in France and Howard Henry Tooth in England.

CMT symptoms commonly include weakness of the foot and lower leg muscles, leading to a high-stepped gait with frequent
tripping and falls. Later in the disease muscle atrophy may spread to the hands.

Researchers led by Klaus-Armin Nave of the Max Planck Institute of Experimental Medicine in Goettingen, Germany, called
the finding a "proof of principle" that they had located a promising target for therapy in CMT, which is not as well
known as other nerve disorders such as ALS - Lou Gehrig's disease.

Although the treatment did not cure the disease, "it improved motor performance," according to the team's report, made
public in Monday's online issue of the journal Nature Medicine.

Their work was welcomed Dr. Craig Blackstone, chief of the cellular neurology unit at the U.S. National Institute of
Neurological Disorders and Stroke.

"They've done what we hope to do with other disease genes," Blackstone said. "They figured out how a gene works and
developed an animal model that mimics the disease ... and then came up with a new, novel way to treat the disease."

There are several forms of CMT.

The most common, CMT-1, accounts for more than half of cases and involves overproduction of the protein Pmp22. That
protein is a vital part of the myelin coating that surrounds nerves. When it is overproduced, the result is an abnormal
nerve sheath.

Production of Pmp22 is stimulated by the hormone progesterone, so Nave's team used onapristone, a progesterone blocker
originally developed for use in breast cancer.

In Nave's experiment the rats treated with onapristone had a 65 per cent improvement in muscle holding ability after
five weeks, compared with rats with CMT left untreated.

Blackstone said that onapristone can have side effects, so it probably would not be useful in humans with CMT. But
other drugs in the same class may work without side effects.

The important thing, he said, is they have shown different method to attack the disease, "something we wouldn't have
thought to do."

This method treats the progression of the disease, rather than just symptoms, and someday could also have uses in
Parkinson's disease and other nerve disorders, he said.

Nave's team agreed that any trials in humans will need to wait until other drugs in the same class are evaluated for
long-term safety. The group also included researchers from the University of Goettingen and the Swiss Federal Institute
of Technology in Zurich.

SOURCE: CTV, Canada
http://tinyurl.com/uf2j

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