Select your localized edition:

Close ×

More Ways to Connect

Discover one of our 28 local entrepreneurial communities »

Be the first to know as we launch in new countries and markets around the globe.

Interested in bringing MIT Technology Review to your local market?

MIT Technology ReviewMIT Technology Review - logo

 

Unsupported browser: Your browser does not meet modern web standards. See how it scores »

Scattered throughout the mammalian menagerie are a few supermuscular freaks: double-muscled cows more ripped than any bodybuilder; racing dogs too burly to run; sheep praised for their massively muscled buttocks; and even one small German boy, born in 2000 with muscles twice the size of those of a normal newborn. All these Herculean creatures share one thing: naturally occurring mutations in a gene that produces myostatin, a protein that blocks growth of skeletal muscle. Disable that gene, and voila–spectacular muscle growth results.

Over the past few years, pharmaceutical companies have been racing to develop ways to mimic myostatin gene mutations in the hope of treating everything from the muscle loss that accompanies muscular dystrophy, cancer, and aging to obesity and other metabolic disorders. Pharmaceutical giants Wyeth and Amgen are expected to release clinical-trial results of myostatin inhibitors for muscle-wasting diseases within the next few months. A smaller company, Acceleron Pharma, based in Cambridge, MA, says that its more broadly acting drug could bring more brawn than can drugs targeting myostatin alone.

“There’s been a huge amount of interest for human therapeutics,” says Se-Jin Lee, a biologist at John’s Hopkins University, in Baltimore. “If you could increase or maintain muscle strength as people age, you could have a tremendous impact on health and well-being.”

Lee discovered more than a decade ago that mice lacking myostatin grew muscles twice the size of those of their normal counterparts. But because mice have levels of myostatin 50 to 80 times that of humans, some scientists have doubted how well the results will translate to humans. New findings published in August in the journal PLoS ONE suggest that other molecules are also at work in muscle. Lee found that he could double the extra growth in mice lacking myostatin–effectively quadrupling muscle mass–by turning up levels of another protein. “That means there must be other regulators that have at least as important a function as myostatin in blocking muscle growth,” says Lee.

Mighty muscles: The image shows the difference between normal mice (left) and mice that lack myostatin and overproduce another protein, giving them four times as much muscle. Scientists are developing drugs that act through similar mechanisms to treat muscle-wasting diseases.
Credit: Se-Jin Lee, Johns Hopkins University School of Medicine

Acceleron’s approach attempts to take advantage of that. Rather than designing an antibody to myostatin itself, as is being tested in the Wyeth trials, scientists at Acceleron fused a portion of the receptor molecule that usually binds to myostatin with a tag that allows the drug ACE-031 to roam freely throughout the body so that it can sop up myostatin before it activates the signal to stop muscle growth. Animal studies show that this approach boosts muscle growth more effectively than does merely eliminating myostatin, suggesting that the fusion molecule also binds to other agents that impact muscle development.

Normal mice given the drug show a 30 to 60 percent increase in muscle mass, and mice with a version of muscular dystrophy show increased grip strength, a standard measure of rodent strength. Preliminary results from primate studies show that the animals on the drug bulk up at similar rates to those seen in rodents. “Before I became involved with Acceleron, if someone had told me you could increase muscle mass by up to 60 percent in a month, I never would have believed it,” says CEO John Knopf.

16 comments. Share your thoughts »

Credit: Stuart Isett, Polaris

Tagged: Biomedicine, genetics, drugs, muscle

Reprints and Permissions | Send feedback to the editor

From the Archives

Close

Introducing MIT Technology Review Insider.

Already a Magazine subscriber?

You're automatically an Insider. It's easy to activate or upgrade your account.

Activate Your Account

Become an Insider

It's the new way to subscribe. Get even more of the tech news, research, and discoveries you crave.

Sign Up

Learn More

Find out why MIT Technology Review Insider is for you and explore your options.

Show Me