Muscle Growth and Myostatin
Myostatin is a protein in humans and animals that regulates muscle
growth. Since 1997, researchers at John Hopkins University have
been studying the effect of myostatin on muscle growth in rats.
Dr. Markus Schuelke, writing in the New England Journal of Medicine,
reports a case of the first known human where a mutant DNA segment
was found to block production of a protein called myostatin that
limits muscle growth.
|The boy has a genetic mutation that boosts
muscle growth. He has twice the muscle and half the fat of other
children his age.
The moment the little boy was born, the hospital staff knew there
was something unusual about him. His muscles were bulging and well
defined, especially in his thighs and upper arms.
At the baby's birth, his doctors were worried. The infant was jittery,
jerking his limbs. After two months, the jerking movements had subsided.
But the puzzle of the baby's muscles remained.
Dr. Schuelke a pediatric neurologist at Charité University
Medical Center in Berlin, had an idea. He knew that Dr. Se-Jin Lee
at Johns Hopkins University, working with mice, had found that when
both copies of a gene for a protein called myostatin were inactivated,
the animals grew up lean and so muscular that Dr. Lee called them
Some researchers are trying to turn off the myostatin gene in chickens
to produce more meat per bird. Cattle breeders stumbled upon the
same genetic trick decades ago. They developed a strain known as
Belgian Blue. The cattle have more muscle and less fat than
other steer. They, too, have inactive myostatin genes.
"We had a big discussion about what to do," Dr. Schuelke
said. "We remembered the mighty mice and the Belgian Blue cattle.
This child looked like that."
The child's mother was strong she had been a professional
sprinter. And she came from a strong family. Her grandfather, a
construction worker, had unloaded curbstones by hand, some weighing
at least 330 pounds.
In other words, the child comes from a "dream pool" of
genetics that apear to have mutated a step further.
Dr. Schuelke and his colleagues decided to test the baby and his
mother for mutations in the myostatin gene. The mother had one nonfunctioning
copy of the gene. In the boy, both copies of the gene were inactive
he was making no myostatin at all.
Muscle cells are surrounded by immature satellite cells that lie
dormant until the muscle is injured. Then they migrate into the
muscle, replacing injured or dead cells. Myostatin might normally
function to keep satellite cells quiescent. Without myostatin, the
satellite cells might be so active building muscle that they become
depleted early in life.
For now, the little boy is healthy and very strong. But what will
happen when he grows older? Will he be an athlete or a bodybuilder?
Or will his satellite cells be used up so that his muscles start
to deflate when he is 30 or so?
The baby's mutation was unusual. Dr. Schuelke and his colleagues
tested 200 people not related to the child and did not find it.
But there are many ways to disable a gene. It's possible that some
naturally strong people have myostatin genes that function poorly,
or not at all.
The findings may help scientists pin down why some people find
it easy to get strong while others can lift weights day after day
to little effect. At least some of this natural variation may be
a result of differences in myostatin levels.
Many scientists believe the find could eventually lead to drugs
for treating people with muscular dystrophy and other muscle-destroying
conditions. And athletes would almost surely want to get their hands
on such a drug and use it like steroids to bulk up.
Given the huge potential market for such drugs, researchers at
universities and pharmaceutical companies already are trying to
find a way to limit the amount and activity of myostatin in the
Drugmaker Wyeth has already begun human tests of a drug designed
to bind to and neutralize myostatin.
The company's first clinical trials of its drug targeting the myostatin
protein are testing whether it is effective against muscular dystrophy
or sarcopenia the loss of muscle mass and strength due to
aging and diseases including cancer. The drug is known only as MYO-029
at this point. The company is not yet projecting when results will
Dr. Lou Kunkel, who is among the doctors participating in the Wyeth
research, thinks success is possible within several years. "Just
decreasing this protein by 20, 30, 50 percent can have a profound
effect on muscle bulk," says Kunkel.
Muscular dystrophy is the world's most common genetic disease.
There is no cure and the most common form, Duchenne's, usually kills
before adulthood. The few treatments being tried to slow its progression
have serious side effects.
Muscle wasting also is common in the elderly and patients with
diseases such as cancer and AIDS.
"If you could find a way to block myostatin activity, you
might slow the wasting process," said Dr. Se-Jin Lee, the Johns
Hopkins professor whose team created the "mighty mice."
Lee believes a myostatin blocker also could suppress fat accumulation
and thus thwart the development of diabetes. Lee and Johns Hopkins
would receive royalties for any myostatin-blocking drug made by
A mystotatin-blocking drug could help other groups of people, including
astronauts and others who lose muscle mass during long stints in
zero gravity or when immobilized by illness or a broken limb.
But it's too soon to know if such drugs will be safe. While the
mice and cattle seem normal, the long-term effects of inhibiting
myostatin aren't known.
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Schuelke, M., Wagner, K.R., Stolz, L.E., Hubner, C., Riebel, T.,
Komen, W., Braun, T., Tobin, J.F., & Lee, S.J. (2004). Myostatin
mutation associated with gross muscle hypertrophy in a child. New
England Journal of Medicine, 350, 2682-2688