Success Boosting Monkey Muscle Could Help Humans
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.
"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.
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MICHELE NORRIS, host:
A few years ago, scientists created a genetically modified mouse with huge muscles. It became known as Mighty Mouse. Now, researchers have used a similar approach to produce muscle-bound monkeys.
As NPR's Jon Hamilton explains, this brings scientists a step closer to new treatments for people with diseases such as muscular dystrophy.
JON HAMILTON: All of this muscle research has to do with a substance called myostatin. Normally, myostatin in the body prevents muscles from getting too big. Take it away and muscles can become huge. So, researchers have been looking for a way to block the effects of myostatin in people with muscle-wasting diseases. You could do that with regular injections of a drug. Another way is to ramp up the body's own ability to block myostatin.
Brian Kaspar of Ohio State University is part of a team that's done that by putting an extra dose of genes right where they're needed.
Dr. BRIAN KASPAR (Professor of Pediatrics, Ohio State University): Our approach has been to develop a one-time gene delivery, given it's a simple shot into the muscle.
HAMILTON: And it works great in mice. But of course, lots of things that work in mice don't work in people.
Jerry Mendell is another member of the gene team. He directs the Center for Gene Therapy at Nationwide Children's Hospital in Columbus.
Dr. JERRY MENDELL (Director, Center for Gene Therapy, Nationwide Childrens Hospital): So, we decided that the best way to test our gene therapy model was to take it to the monkey. And if it worked, it had a better chance of working in patients.
HAMILTON: The team injected the right thigh muscles of six macaque monkeys. Kaspar says researchers didn't have to wait long.
Dr. KASPAR: We found that muscles started to get larger in circumference. And when we measured the strength generated out of those muscles, indeed the treated muscles were significantly higher than untreated muscles.
HAMILTON: The success means the team is ready to move on to people. Mendell says they want to begin with patients who have a disease called inclusion body myositis. It leaves thigh muscles so weak, people can't stand up.
Dr. MENDELL: If everything works out, we should be in a clinical trial by next summer.
HAMILTON: That would be a big step. But even cautious scientists have been impressed by the results in monkeys.
Dr. SE-JIN LEE (Professor of Molecular Biology and Genetics, Johns Hopkins University): Certainly very intriguing, very interesting, potentially very exciting.
HAMILTON: That's Se-Jin Lee of Johns Hopkins University. He's the scientist who discovered myostatin. Lee says many different groups have now found ways to manipulate the myostatin pathway and produce muscle growth in a wide range of animals. He says that bodes well for treating people.
Dr. LEE: Tampering with this pathway will probably work in terms of increasing muscle growth. You know, that still is hypothesis. It definitely has not been proven, but there are more and more signs that that probably will work.
HAMILTON: And not just on sick people. Athletes and bodybuilders have been following the research closely. Some of them are looking for a new kind of doping. Lee says it would be pretty hard for these would-be dopers to make drugs that block myostatin.
Dr. LEE: The scary part is that that's just not true in the case of gene therapy. It's a fairly easy thing for a, you know, a small group to set up and produce, and you only need to give essentially a single injection, presumably, or a limited number of injections and it's there forever.
HAMILTON: The World Anti-Doping Agency is already working on a test for this sort of doping. The new research appears in the journal Science Translational Medicine.
Jon Hamilton, NPR News. Transcript provided by NPR, Copyright National Public Radio.
