Myostatin Research Paper
BOSTON — Somewhere in Germany is a baby Superman, born in Berlin with bulging arm and leg muscles. Not yet 5, he can hold seven-pound weights with arms extended, something many adults cannot do. He has muscles twice the size of other kids his age and half their body fat.
DNA testing showed why: The boy has a genetic mutation that boosts muscle growth.
The discovery, reported in Thursday’s New England Journal of Medicine, represents the first documented human case of such a mutation.
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. …show more content…
The boy’s mutant DNA segment was found to block production of a protein called myostatin that limits muscle growth.
The news comes seven years after researchers at Johns Hopkins University in Baltimore created buff “mighty mice” by “turning off” the gene that directs cells to produce myostatin.
“Now we can say that myostatin acts the same way in humans as in animals,” said the boy’s physician, Dr. Markus Schuelke, a professor in the child neurology department at Charite/University Medical Center Berlin. “We can apply that knowledge to humans, including trial therapies for muscular dystrophy.”
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 body. Wyeth has just begun human tests of a genetically engineered antibody designed to neutralize myostatin.
Dr. Lou Kunkel, director of the genomics program at Boston Children’s Hospital and professor of pediatrics and genetics at Harvard Medical School, said success is possible within several years.
“Just decreasing this protein by 20, 30, 50 percent can have a profound effect on muscle bulk,” said Kunkel, who is among the doctors participating in the Wyeth
research.
Slow wasting process
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 said he 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 Wyeth.
Dr. Eric Hoffman, director of Children’s National Medical Center’s Research Center for Genetic Medicine, said he believes a muscular dystrophy cure will be found, but he is unsure whether it will be a myostatin-blocking drug, another treatment or a combination, because about a dozen genes have some effect on muscles.
He said 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.
Eventual health problems?
Researchers would not disclose the German boy’s identity but said he was born to a somewhat muscular mother, a 24-year-old former professional sprinter. Her brother and three other close male relatives all were unusually strong, with one of them a construction worker able to unload heavy curbstones by hand.
In the mother, one copy of the gene is mutated and the other is normal; the boy has two mutated copies. One almost definitely came from his father, but no information about him has been disclosed. The mutation is very rare in people.
The boy is healthy now, but doctors worry he could eventually suffer heart or other health problems.
In the past few years, scientists have seen great potential in myostatin-blocking strategies.
Internet marketers have been hawking “myostatin-blocking” supplements to bodybuilders, though doctors say the products are useless and perhaps dangerous.
Some researchers are trying to turn off the myostatin gene in chickens to produce more meat per bird. And several breeds of cattle have natural variations in the gene that, aided by selective breeding, give them far more muscle and less fat than other steer.
He could do the iron cross when he was 5 months old," said his adoptive mother, Dana Hoekstra of Roosevelt Park. She was referring to a difficult gymnastics move in which a male athlete suspends himself by his arms between two hanging rings, forming the shape of a cross.
Liam has the kind of physical attributes that bodybuilders and other athletes dream about: 40 percent more muscle mass than normal, jaw-dropping strength, breathtaking quickness, a speedy metabolism and almost no body fat.
Liam can run like the wind, has the agility of a cat, lifts pieces of furniture that most children his age couldn't push across a slick floor and eats like there is no tomorrow -- without gaining weight.
Liam Hoekstra was hanging upside down by his feet when he performed an inverted sit-up, his shirt falling away to expose rippled abdominal muscles. It was a display of raw power one might expect to see from an Olympic gymnast. Liam is 19 months old.
The so-called myostatin blockade has generated tremendous interest in the bodybuilding community. Some nutritional supplements claim to block myostatin, but researchers have said the claims are not scientifically valid.
"If the myostatin protein is knocked out, muscles grow and rejuvenate much more quickly," Dr. Larson said. "It has potential for great abuse in the future as the new steroid."
[Despite being born to a troubled mother who gave him up for adoption at birth and Liam being born with a suite of medical problems not related to the muscle genes.] Liam being born four weeks early and had a small hole in his heart. He also had eczema, enlarged kidneys, was lactose intolerant and had severe stomach reflux that made him vomit several times each day, his mother said. Two days after he was born, Liam could stand up and support his weight if someone held his hands to provide balance.
His is one of roughly 100 known cases in the world, according to experts and medical literature.
Myostatin (also known as growth differentiation factor 8) is a secreted TGF beta protein family member that inhibits muscle differentiation and growth. Myostatin is produced primarily in skeletal muscle cells, circulates in the blood and acts on muscle tissue, by binding a cell-bound receptor called the activin type II receptor.[1][2] In humans, myostatin is encoded by the MSTN gene.[3]
The gene encoding myostatin was discovered in 1997 by geneticists Alexandra McPherron and Se-Jin Lee who also produced a strain of mutant mice that lack the gene. These myostatin "knockout" mice have approximately twice as much muscle as normal mice.[5] These mice were subsequently named "mighty mice".
Naturally occurring myostatin "nulls" have been identified in cattle, whippets, and humans; in each case the result is a dramatic increase in muscle mass. A mutation in the the 3' UTR of the myostatin gene in Texel sheep creates target sites for the microRNAs miR-1 and miR-206. This is likely to cause the muscular phenotype of this breed of sheep.[6]
DNA testing showed why: The boy has a genetic mutation that boosts muscle growth.
The discovery, reported in Thursday’s New England Journal of Medicine, represents the first documented human case of such a mutation.
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. …show more content…
The boy’s mutant DNA segment was found to block production of a protein called myostatin that limits muscle growth.
The news comes seven years after researchers at Johns Hopkins University in Baltimore created buff “mighty mice” by “turning off” the gene that directs cells to produce myostatin.
“Now we can say that myostatin acts the same way in humans as in animals,” said the boy’s physician, Dr. Markus Schuelke, a professor in the child neurology department at Charite/University Medical Center Berlin. “We can apply that knowledge to humans, including trial therapies for muscular dystrophy.”
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 body. Wyeth has just begun human tests of a genetically engineered antibody designed to neutralize myostatin.
Dr. Lou Kunkel, director of the genomics program at Boston Children’s Hospital and professor of pediatrics and genetics at Harvard Medical School, said success is possible within several years.
“Just decreasing this protein by 20, 30, 50 percent can have a profound effect on muscle bulk,” said Kunkel, who is among the doctors participating in the Wyeth
research.
Slow wasting process
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 said he 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 Wyeth.
Dr. Eric Hoffman, director of Children’s National Medical Center’s Research Center for Genetic Medicine, said he believes a muscular dystrophy cure will be found, but he is unsure whether it will be a myostatin-blocking drug, another treatment or a combination, because about a dozen genes have some effect on muscles.
He said 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.
Eventual health problems?
Researchers would not disclose the German boy’s identity but said he was born to a somewhat muscular mother, a 24-year-old former professional sprinter. Her brother and three other close male relatives all were unusually strong, with one of them a construction worker able to unload heavy curbstones by hand.
In the mother, one copy of the gene is mutated and the other is normal; the boy has two mutated copies. One almost definitely came from his father, but no information about him has been disclosed. The mutation is very rare in people.
The boy is healthy now, but doctors worry he could eventually suffer heart or other health problems.
In the past few years, scientists have seen great potential in myostatin-blocking strategies.
Internet marketers have been hawking “myostatin-blocking” supplements to bodybuilders, though doctors say the products are useless and perhaps dangerous.
Some researchers are trying to turn off the myostatin gene in chickens to produce more meat per bird. And several breeds of cattle have natural variations in the gene that, aided by selective breeding, give them far more muscle and less fat than other steer.
He could do the iron cross when he was 5 months old," said his adoptive mother, Dana Hoekstra of Roosevelt Park. She was referring to a difficult gymnastics move in which a male athlete suspends himself by his arms between two hanging rings, forming the shape of a cross.
Liam has the kind of physical attributes that bodybuilders and other athletes dream about: 40 percent more muscle mass than normal, jaw-dropping strength, breathtaking quickness, a speedy metabolism and almost no body fat.
Liam can run like the wind, has the agility of a cat, lifts pieces of furniture that most children his age couldn't push across a slick floor and eats like there is no tomorrow -- without gaining weight.
Liam Hoekstra was hanging upside down by his feet when he performed an inverted sit-up, his shirt falling away to expose rippled abdominal muscles. It was a display of raw power one might expect to see from an Olympic gymnast. Liam is 19 months old.
The so-called myostatin blockade has generated tremendous interest in the bodybuilding community. Some nutritional supplements claim to block myostatin, but researchers have said the claims are not scientifically valid.
"If the myostatin protein is knocked out, muscles grow and rejuvenate much more quickly," Dr. Larson said. "It has potential for great abuse in the future as the new steroid."
[Despite being born to a troubled mother who gave him up for adoption at birth and Liam being born with a suite of medical problems not related to the muscle genes.] Liam being born four weeks early and had a small hole in his heart. He also had eczema, enlarged kidneys, was lactose intolerant and had severe stomach reflux that made him vomit several times each day, his mother said. Two days after he was born, Liam could stand up and support his weight if someone held his hands to provide balance.
His is one of roughly 100 known cases in the world, according to experts and medical literature.
Myostatin (also known as growth differentiation factor 8) is a secreted TGF beta protein family member that inhibits muscle differentiation and growth. Myostatin is produced primarily in skeletal muscle cells, circulates in the blood and acts on muscle tissue, by binding a cell-bound receptor called the activin type II receptor.[1][2] In humans, myostatin is encoded by the MSTN gene.[3]
The gene encoding myostatin was discovered in 1997 by geneticists Alexandra McPherron and Se-Jin Lee who also produced a strain of mutant mice that lack the gene. These myostatin "knockout" mice have approximately twice as much muscle as normal mice.[5] These mice were subsequently named "mighty mice".
Naturally occurring myostatin "nulls" have been identified in cattle, whippets, and humans; in each case the result is a dramatic increase in muscle mass. A mutation in the the 3' UTR of the myostatin gene in Texel sheep creates target sites for the microRNAs miR-1 and miR-206. This is likely to cause the muscular phenotype of this breed of sheep.[6]