Science Translational Medicine
This microscopic image of monkey muscle cells from the study shows how cells treated with gene therapy to spur growth (right) gained enhanced muscle mass and strength.
This microscopic image of monkey muscle cells from the study shows how cells treated with gene therapy to spur growth (right) gained enhanced muscle mass and strength. Science Translational Medicine
Scientists are a step closer to finding a treatment for people with diseases like muscular dystrophy, thanks to some muscle-bound monkeys.
The monkeys grew bigger thigh muscles after receiving a type of gene therapy, according to a new study published in the journal Science Translational Medicine.
Because monkeys are genetically similar to humans, the success means this sort of gene therapy is likely to work on people too.
The muscle research involves a protein called myostatin that occurs naturally in the body. Normally, myostatin prevents muscles from getting too big. But when it's removed or its action is blocked, muscles can become huge.
Earlier research showed that mice lacking the gene for myostatin develop muscles more than twice as large as normal mice.
So researchers have been looking for a way to block the effects of myostatin in people with disorders that cause their muscles to waste away. They've been able to do this with regular injections of a drug, but these don't change the muscle permanently.
Another way is to ramp up the body's own ability to block myostatin, says Brian Kaspar of Ohio State University and Nationwide Children's Hospital in Columbus.
Kaspar is part of a team that has inserted a gene into muscles that ramps up production of a protein called follistatin. The protein is a powerful inhibitor of myostatin.
The technique worked well in mice. But lots of things that work in mice don't work in people, says Jerry Mendell, who directs the Center for Gene Therapy at the Research Institute at Nationwide.
Science Translational Medicine
This monkey from the study was treated with the gene therapy for building muscle mass in his right leg (the arrows point to the injection sites). The photo was taken five months after the monkey started receiving the injections of follistatin and shows how the right leg muscle had already started to bulk up compared with the left.
This monkey from the study was treated with the gene therapy for building muscle mass in his right leg (the arrows point to the injection sites). The photo was taken five months after the monkey started receiving the injections of follistatin and shows how the right leg muscle had already started to bulk up compared with the left. Science Translational Medicine
"So we decided that the best way to test our gene therapy model was to take it to the monkey," Mendell says.
The team injected the right thigh muscles of six macaque monkeys. Within a few months, they began to see changes.
"We found that the muscles started to get larger in circumference," Kaspar says. And tests showed that the treated muscles also became stronger than untreated muscles.
Hope For People
The success means the team is ready to move on to people. Researchers want to begin with patients who have a disease called inclusion body myositis, Mendell says. It leaves thigh muscles so weak people can't stand up.
"If everything works out we should be in a clinical trial by next summer, Mendell says.
That would be a big step. But groups that support research on muscle diseases say they're anxious to make that step possible.
The Myositis Association has already helped fund the animal research. And a spokesman for the Muscular Dystrophy Association, which has supported both Mendell's and Kaspar's work, says the group hopes to help fund the first trials in people.
"It's exciting to see profound improvement in muscle size and strength with no adverse effects on any organs or systems," said Dr. R. Rodney Howell, chairman of the MDA Board of Directors, in a statement.
Other scientists are also impressed by the results in monkeys.
"It's potentially very exciting," says Se-Jin Lee of Johns Hopkins University, who discovered the myostatin gene.
Lee says he's optimistic that a treatment will emerge because so many different groups have now found ways to manipulate the myostatin pathway and produce muscle growth in a wide range of animals.
"There are more and more signs that this will probably work," he says.
Guarding Against Misuse Of New Treatment
And if it does, the muscle-building effects won't be limited to sick people. So it's no surprise that athletes and bodybuilders have been following the research closely.
And it's clear that some people want to use any new treatments to enhance athletic performance, Lee says.
Drugs that block myostatin are pretty hard for would-be dopers to produce on their own, Lee says. But he adds that gene therapy is less of a challenge.
"It's a fairly easy thing for a small group to set up and produce," he says. And once a gene is introduced into a muscle, he says, it's there forever.
The World Anti-Doping Agency is also concerned. It's already funding work on tests to detect doping that affects the myostatin system.