Skeletal-muscle Atrophy 'switch' Discovered by Purdue Researchers!

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Purdue Researchers Find 'switch' For Skeletal-muscle Atrophy

http://www.medicalnewstoday.com/medicalnews.php?newsid=43984

Researchers in Purdue University's School of Veterinary Medicine have

discovered genetic and drug-treatment methods to arrest the type of

muscle atrophy often caused by muscle disuse, as well as aging and

diseases such as cancer.

The findings might eventually benefit people who have been injured or

suffer from diseases that cause them to be bedridden and lose muscle

mass, or sometimes limbs, due to atrophy, said Amber Pond, a research

scientist in the school's Department of Basic Medical Sciences.

" The weight loss and muscle wasting that occurs in patients with

cancer or other diseases seriously compromises their well-being and

is correlated with a poor chance for recovery, " Pond said. " In

addition, muscle weakness caused by atrophy during aging can lead to

serious falls and bone loss. Exercise is the most beneficial strategy

to treat atrophy. However, many individuals are too ill to adequately

participate in exercise programs.

" We've found a chemical 'switch' in the body that allows us to turn

atrophy on, and, from that, we also have learned how to turn atrophy

off. "

Findings based on the research, funded in large part by the American

Heart Association, are detailed in a study available online today

(Wednesday, May 24) in The FASEB Journal, published by the Federation

of American Societies for Experimental Biology. The study will be in

the journal's print edition in July.

The research team found atrophy of skeletal muscle in mice could be

inhibited with both gene therapy and drug treatment using astemizole

(as-TEM-uh-zole), an antihistamine. This new insight has potential in

many different areas of research, Pond said.

" We have discovered a direct link between atrophy and a protein in

the skeletal muscle, " Pond said. " This led us to develop methods that

would block the protein's ability to cause atrophy. Through drug

treatment, we were able to block atrophy, allowing muscle to retain

97 percent of its original fiber size in the face of atrophy. "

Astemizole, which was withdrawn from the market in 2000 because of

its potential to cause serious cardiovascular problems, wouldn't be

suitable for use in humans, Pond said. The drug can be used in mice

because it doesn't affect their hearts to the same extent.

" Astemizole administration to humans poses too great a risk, " Pond

said. " There's a need for more study to avoid those side effects, but

the key is that we found a protein capable of sensing muscle disuse

and initiating atrophy. "

In the drug study, researchers used four groups of mice: a control

group, a second group that was given astemizole, and two additional

groups in which muscle atrophy was introduced. One of these two

groups received astemizole while the second did not. Both of these

groups were placed in cages constructed to elevate them so that they

were unable to place any weight on their back legs.

" Use of the custom cages to produce atrophy was established in

the '80s for simulation of NASA space flight; you can't mimic these

effects on muscle and bone in cell culture, " said Hannon,

associate professor of developmental anatomy and one of the study's

authors. " The mice were able to move around the cage and eat and

drink on their own. We monitored their food and water intake and

overall health and ensured that they were playing and eating

normally. "

This method allowed the scientists to demonstrate the effects of

skeletal muscle atrophy and investigate reasons for the link with the

Merg1a protein. The Merg1a protein is a channel that normally passes

a small electrical current across the cell.

The researchers implanted a gene into the skeletal muscle that

resulted in a mutant form of this protein that combines with the

normal protein and stops the current. The researchers found that the

mutant protein would inhibit atrophy in mice whose ability to use

their back legs was limited.

Because gene therapy is not yet a practical treatment option in

humans, the researchers decided to go a step further and stop the

function of the protein with astemizole, which is a known " Merg1a

channel blocker. " The researchers found that the drug produced

basically the same results as the gene therapy. In fact, muscle size

increased in mice in the group that were given the drug without any

other treatment.

" We are now looking at the differences in the structure of the heart

and the skeleton to give us clues on how to specifically target

muscles without the cardiac side effects, " Pond said.