Muscular 4-year-old may power medical advances

The Associated Press and The Baltimore Sun

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DNA testing showed why: The boy has a genetic mutation that boosts muscle growth.

The discovery, reported in today's New England Journal of Medicine, has given researchers knowledge that could lead to breakthrough therapies for muscular dystrophy and other diseases, perhaps even for diabetes and obesity. The potential treatments, involving myostatin, a protein that controls muscle growth, also could have a dark side, giving athletes another illicit chemical means to boost their performance.

The boy's body produces no myostatin. Researchers knew that the protein regulates muscle in animals, but this was the first time it has been shown to affect humans. The study raises hopes that myostatin-blocking treatments could encourage muscle growth.

"It's a huge step," said Johns Hopkins University geneticist Se-Jin Lee, one of the study's authors. "Based on animal studies, we thought it worked in humans. But there was lingering uncertainty."

Since Lee and another Hopkins researcher discovered myostatin seven years ago, scientists have studied the chemical as a potential treatment for diseases that destroy muscle.

Most have focused on muscular dystrophy, a genetic illness that progressively damages skeletal muscle. There is no effective treatment, and most patients die in their 20s from a combination of heart and breathing problems.

A 2002 study found that mice with a version of the disease improve after being given myostatin blockers. By confirming myostatin's effect on humans, the new study will spur more research, Lee said.

"It's a big step," said Dr. Elizabeth McNally, a muscular-dystrophy specialist at the University of Chicago.

Wyeth Pharmaceuticals already has created a protein that disables myostatin, and is beginning a human safety trial of the substance, known as MYO-029. The company, which has a patent on all human therapeutic uses of myostatin, also is planning a study with muscular-dystrophy patients.

"There's a big medical opportunity in this," said Wyeth biochemist James Tobin, who is overseeing the research. Tobin also was involved in the study of the German boy.

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.

The child's condition was discovered the day he was born, when a doctor became concerned that the infant's unusually well-defined muscles might be a sign of illness.

Pediatric neurologist Markus Scheulke examined the boy and found him normal, but he had read one of Lee's myostatin papers and wondered whether the infant had an abnormal myostatin gene. Tests confirmed his suspicion, and Schuelke contacted Lee and Wyeth about his discovery.

Doctors at first worried that the absence of myostatin would cause physical problems, perhaps impairing the boy's heart. But he seems normal, except for his physique and strength. "He has very large muscles," Lee said.

The condition is inherited, at least in part: His mother, 24, was a professional sprinter, and several other family members are muscular.

Doctors believe myostatin blockers could treat other muscle-related diseases, including an age-related muscle loss known as sarcopenia and an aggressive variant called cachexia that afflicts cancer and HIV patients, among others. Researchers also have found lowering myostatin levels in mice significantly decreases obesity and improves symptoms of Type 2 diabetes.

Hoffman said a myostatin-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.

Unknowingly, humans have been modifying myostatin genes for more than a century in several varieties of beef cattle known for their bulging muscles and lack of fat. In tests, these "double-muscled" breeds, which include Belgian Blue and Piedmontese, displayed an altered myostatin gene and produce almost none of the substance.

If they work on humans, myostatin blockers almost certainly will find another use — as an athletic performance booster. Researchers say such compounds likely would provide a significant advantage.

"It's going to have a lot less side effects than steroids, and probably bigger effects on muscles," said University of Pennsylvania physiologist H. Lee Sweeney, who studies a related hormone called IGF-1, which spurs muscle growth.

Despite the illicit potential, scientists emphasize that myostatin blockers would help many desperate patients. Said Lee: "There are people in dire need."

Copyright © 2004 The Seattle Times Company

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