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.
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.
‘Improved motor performance'
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.
“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 percent 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.
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. It affects nearly 120,000 Americans, compared with about 20,000 who have the better-known Lou Gehrig’s disease.
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.