In 1997, scientist Se-Jin Lee genetically engineered "Mighty Mice" with twice as much muscle as regular rodents. Now, pharmaceutical companies are using his discovery to make drugs that could help elderly patients walk again and rebuild muscle in a range of diseases.
Novartis AG, working with biotech company MorphoSys AG, has the most advanced of these. Sanofi, Eli Lilly & Co., GlaxoSmithKline PLC, Pfizer Inc. and closely held Atara Biotherapeutics are working on earlier-stage drugs. They are all in clinical or earlier-stage testing; the first could be approved in 2016.
"I am very optimistic about these new drugs," says Dr. Lee, a professor of molecular biology at Johns Hopkins University in Baltimore, who isn't involved in any of the drug trials.
"The fact that they're so far along means to me they must have seen effects."
Myostatin is a naturally occurring protein that curbs muscle growth. The drugs act by blocking it, or blocking the sites where it is detected in the body, potentially rebuilding muscle.
"I think the enthusiasm around myostatin is quite clear," says Nathan LeBrasseur, an associate professor and muscle specialist at the Mayo Clinic in Rochester, Minn. "If you were to ask for the perfect drug target, it's hard to argue against myostatin because it's so unique to skeletal muscle."
The ultimate prize for these drugs would be in treating the elderly.
Experts say muscle wasting and Alzheimer's—the decline in physical and cognitive functions, respectively—are the two major causes of institutionalization among the elderly.
One of the most important aspects of aging is frailty, which means you slow down and become weaker. "A lot of that is due to muscle strength, which we are looking to improve," says Mark Fishman, head of the Novartis Institutes for Biomedical Research.
Novartis and Sanofi are both testing their drugs in age-related muscle wasting, called sarcopenia. Lilly is testing its drug in elderly patients undergoing hip replacements or those recovering from falls.
"However you cut it, muscle wasting that has an impact on function is a very, very large patient population," says Bill Evans, a specialist in aging and muscle-metabolism at GlaxoSmithKline.
"It really depends where the regulators put the cutoff point, but my guess is it could affect 15% to 20% of the population over the age of 65 or 70."
Still, there are major hurdles to getting a sarcopenia drug approved. Regulators haven't yet defined sarcopenia as a disease, meaning there is no easy way to approve a drug to treat it.
"People tend to look at muscle loss as something that's just an inevitable process of aging," says Dr. Lee.
Drug companies also fear the herculean task of recruiting thousands of elderly patients—preferably not on other medications—for expensive, multiyear clinical trials.
"I think a number of companies have pulled out because there's not the grand-slam home run," says Dr. Evans.
Another concern is misuse, by athletes, bodybuilders or by those looking for an antiaging elixir, even when muscle wasting isn't the problem.
"If you think your mother can be kept out of a nursing home by using a compound—I think there's going to be a pretty large demand for something like that," he adds.
The drugs are still some way off being approved to treat elderly patients. But Dr. Lee is eager to see any medical application for his discovery, after a series of myostatin drug failures in the late 2000s.
Wyeth, now part of Pfizer, and U.K. drug group Shire PLC, in partnership with Acceleron Pharma Inc., both stopped myostatin drugs in development for muscular dystrophy.
Patients in Shire trials showed some unexplained nose and gum bleeding. Planned trials by Amgen Inc. and others were halted.
Myostatin drugs got an "early blemish," says Dr. LeBrasseur. The new treatments work in a slightly different way.
Hopes for Novartis's drug BYM338 are now high. Analysts estimate peak annual sales of $4.9 billion, according to a study compiled by consultancy Defined Health, cited by MorphoSys. J.P. Morgan analysts give an estimate off $3.4 billion.
The most advanced testing of BYM338 is in patients with a rare muscle-wasting disease called sporadic inclusion-body myositis. In trials, patients showed a small increase in their thigh muscle volume, and were able to walk farther than those taking a placebo, although the effects waned after treatment.
BYM338 is now in the late stages of clinical testing in the disease, with data from another trial expected in late 2015. Drugs for rare diseases can gain swift approval after relatively small trials.
Myostatin drugs are also being tested for muscle wasting caused by a chronic illness—a condition called "cachexia." That would be a far larger market.
By some estimates, cachexia is responsible for nearly a third of cancer deaths, as well as leading to the deaths of tuberculosis, heart-disease and lung-disease patients. Current appetite-stimulant treatments aren't always effective, and steroids can have bad side effects.
Others think the drugs could even be used to treat obesity and Type 2 diabetes one day, since building more muscle means a bigger storage area for sugars that might otherwise accumulate in the liver or pancreas.
Building muscle also increases the body's need for calories, which means patients burn off more of the food they eat.
"There's not a single drug on the market today that targets muscle growth in diabetics," says Dr. LeBrasseur. "That's pretty profound when you think of muscle playing such a key role in metabolism."
Still, he cautions there is a lot of work ahead.
"One thing we don't understand yet is why myostatin is released from muscle—is it playing an important role in other organ health? I think it's great we're going after this as a drug target, I just feel like we need to understand the biology a little bit better."