May 25, 2006
Protein Target Found To Block Muscle Atrophy

A drug and a gene therapy can block muscle atrophy in mice which get little exercise.

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.


"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."

A protein called Merg1a plays a key role in allowing or blocking muscle atrophy and atrophy can be blocked by an antihistamine which targets Merg1a and also by gene therpy.

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Astemizole, which was withdrawn from the market in 2000 because of its potential to cause serious cardiovascular problems, wouldn't be suitable for use in humans, Pond said.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.

While the drug used in the experiment isn't suitable for human use this discovery points toward a direction for drug development to prevent muscle atrophy with cancer, age, or low exercise.

A mutant form of Merg1a inserted with gene therapy prevented muscle atrophy in low exercise mice.

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.

A lot of people would love to have the effects of exercise last longer. Also, a method to avoid muscle atrophy with age would have very wide appeal.

Share |      Randall Parker, 2006 May 25 12:19 AM  Biotech Manipulations

CASpears said at May 25, 2006 4:27 AM:

The first thing I thought of when I read this is...extended space travel to places like Mars or the moons of Jupiter.

PacRim Jim said at May 25, 2006 12:06 PM:

You vill tell Ahnold, no?

Robert Silvetz said at May 25, 2006 4:50 PM:

Makes one wonder how this would dovetail with myostatin inhibition? If we genetically engineered humans with decreased myostatin expression while modifying Merg1a... do we end up with well-muscled men and women that don't have to excersize significantly to maintain their muscle masses? And wouldn't that be an incredible boon running into the elderly years? (Unless SENS does away with ageing...)

Randall Parker said at May 25, 2006 5:13 PM:

PacRim Jim,

Ve vill Pump You Up With Gene Therapy! Gene therapy will do away with girlie men!

Robert Silvetz,

I'm thinking that gene therapy intervening at the right point in the regulatory process could boost muscle mass with less threat of cancer or premature aging than probably comes from using growth hormone.

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