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'MIGHTY MOUSE' TO AID OF MEDICINE

‘Monster’ gene defect may counter deadly affliction

by Rowan Hooper

Want to have huge muscles but are too lazy to go to the gym? There could soon be a way.

In 2004, a young German boy was taken to the doctor by his mother, a former sprinter. At age 3, the boy was already incredibly strong and had the muscle development of a weightlifter. The muscles in his upper arms and legs were twice as big as other children’s.

Doctors found that the boy had two defective copies of the myostatin gene. His mother, it turned out, had one defective copy, a mutation that had clearly helped in her athletic career.

Myostatin is the gene that limits muscle growth. Without it, muscles grow abnormally. When its production is blocked in genetically altered mice, the animals develop twice the usual amount of muscle. The gene’s nickname? Mighty Mouse.

But it’s not just mice. The Belgian Blue and Piedmont breeds of cattle have been bred to preserve a naturally occurring defective myostatin gene, and they develop 25 percent more muscle. Their bodies are highly sculpted and they are sometimes called “monster cows.” Some countries, including Sweden, don’t allow them to be farmed.

Without myostatin in the body, fat is not accumulated in the normal way. In monster cows this means the meat is very lean. Now, researchers are looking into ways that this effect could be used to treat obesity. In obese mice, for example, blocking the production of myostatin leads to dramatic weight loss.

Myostatin is also being used in research aimed at treating muscular dystrophy. There are several kinds of dystrophies, all of them genetic diseases that cause defects in muscle proteins and progressive muscular death. People with the disease have problems walking, they feel weak and suffer muscular wasting. There is no known cure, and in some forms (such as Duchenne muscular dystrophy) death commonly occurs when the victim is in their 20s.

The idea behind this research is to make a drug that blocks myostatin and boosts muscle growth, canceling out the effect of the wasting disease. Of course, that drug would be very attractive to athletes hoping to squeeze more power from their muscles, as well as for those of us too slovenly to get down to the gym.

Fake drugs purporting to be myostatin blockers are already being sold on the Internet. However, if and when a genuine myostatin-blocking drug is developed, there will be a few things casual users will have to bear in mind.

First, nothing comes for free. The cost of extra muscle can be counted in metabolic terms. Anyone blocking their myostatin will develop a large appetite, especially for protein.

Second, as the muscle is piled on, the forces exerted on the skeletal system will increase. Even people with normal myostatin can suffer broken bones due to muscle contractions. For instance, psychiatric patients receiving electroshock therapy (ECT) need to be given curare, a muscle relaxant, prior to the treatment. Without it, the convulsions induced by ECT can result in bone fractures. Bone breakages would be more common in people blocking myostatin, so bones and tendons would have to be fortified accordingly. Bones would have to be strengthened with titanium, which is hardly convenient.

Third, blocking mysostatin might cause some muscles to increase that should really remain a normal size. If the heart or some other organ gets too big, it could be dangerous. For this reason doctors are monitoring what happens with the German boy. At present, his health is unaffected by his mutation — but athletes and bodybuilders taking drugs purporting to block myostatin are nonetheless still taking a risk.

While we wait for scientists to develop the drug and test it properly, there are other ways to stimulate muscles that aren’t responsive.

At Hokkaido University in Sapporo, a researcher developed a technique to help people walk who had been paralyzed by strokes. Wenwei Yu made an implant that uses signals from a healthy leg to stimulate a paralyzed one. He placed sensors over certain muscle groups on the healthy legs of men who had suffered strokes, and stimulators on their paralyzed legs. The sensors monitor signals from the patient’s able leg and are used to trigger preprogrammed electrical impulses in 11 electrodes implanted near nerves in the paralyzed leg. This lets the paralyzed leg do what the patient wants it to do by taking its cue from the good leg. Yu says it will be another couple of years before his technology becomes generally available.