Myostatin?

[mark000]

For a few years there have been reports in the scientific media about myostatin inhibitors as a way to overcome normal limits to muscle development.
Below is the beginning of a new online report in MIT's Technology Review.

http://www.technologyreview.com/Biotech/19589/?nlid=610

Since the time this was first being reported (eg Science News, Nov 22 1997), powerlifting records have gone through the roof.

As a non-athlete, I have no knowledge of who takes what, but I wonder, without naming names, whether any BBers or other athletes have been experimenting with this pathway.

"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 viola--spectacular muscle growth results."

http://www.technologyreview.com/files/13395/whippet_x220.jpg

[Scott]

hey mark did u adopt one of Vick's dawgs? j/k ;)

[mark000]

The dog photo is from Technology Review online, I doubt that they would resort to Photoshop.

Here is the caption:
Bully whippet:
The dog in the photo is supermuscular because of naturally occurring mutations that silence both versions of the myostatin gene. Called bully whippets, these dogs are rarely champion racers. However, animals with one mutated and one normal version of the gene are more muscular than typical animals and are among the breed’s fastest racers.
Credit: Stuart Isett, Polaris

[James]

sheep praised for their massively muscled buttocks;

:sheep2: Finally we have a use for this smiley! (note to self: avoid men who praise sheep with 'massively muscled buttocks')

[James]

If I'm reading that correctly, that dog is naturally muscular like that. It was not genetically altered?

[CalJoe]

If I'm reading that correctly, that dog is naturally muscular like that. It was not genetically altered?
I can't tell if the article is saying that this dog was administered myostatin, or if the dog had undergone a series of myostatic mutations. Either way it is very compelling evidence of the still untapped potential that this type of research and development is capable of. It should be noted, however, that according to the article mice have a natural recurring myostatic level that is 50 to 80 times more than humans, leaving speculation as to whether humans can undergo such a dramatic change. That being said, the introduction of any agent that would add even 5% muscle mass to what would be considered a maxed out physique is very significant. This would be like taking a male IFBB pro that competes at 3% bodyfat at 240 pounds and suddenly adding 10-12 pounds at the same bodyfat percentage. The change onstage would be dramatic.

[ibarramedia]

Believe it or not guys that dog is a FEMALE dog... I think Nadia Nardi even met that dog once.

[mark000]

I can't tell if the article is saying that this dog was administered myostatin, or if the dog had undergone a series of myostatic mutations.

The caption says "The dog in the photo is supermuscular because of naturally occurring mutations that silence both versions of the myostatin gene."

The mutation apparently occurs naturally. The article cites a newborn human "with muscles twice the size of those of a normal newborn." Other articles, including a cover story in Scientific American a few years back, show pictures of a breed of cattle called Belgian Blue that looks like bovine BBs. (BBBBBs?)

Apparently research on drugs to produce these effects has been ongoing for years.

"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."

My question is: has such R&D has been going on in the performance enhancement underground, or is there another explanation for the dramatic increase in powerlifing records, for example, over the same period?

[Echo]

Research regarding myostatin, and myostatin inhibition, has been going on for quite some time and has potential therapeutic application in muscular dystrophy, muscle atrophy following injury/immobilization, and AIDS. Michael Zumpano, CEO and President of Champion Nutrition has been studying nutritional approaches which might influence myostatin to a slight degree and has launched at least one such product.

As usual, some of the most interesting information for bodybuilders is coming from AIDS research. Understanding why people with AIDS develop wasting over the course of HIV disease has been of great interest for many years. While recent investigations seem to center on the metabolic complications of patients on highly active antiretroviral therapy (HAART), researchers have long believed that cytokine and growth factor dysregulation are responsible for AIDS wasting, with loss of lean body mass and muscular atrophy.

Yarasheski and colleagues from Washington University in St. Louis and Charles R. Drew University in Los Angeles, recently presented data on myostatin, a muscle-specific growth and differentiation factor (GDF-8) expressed by a recently discovered gene within the TGF-beta superfamily which appears to suppress muscle growth. In "knockout mice," underexpression of myostatin resulted in muscles three times larger than wild-type mice. Similar experiments have been carried out and exploited by the agricultural community on chickens and cows. Nonetheless, seeing the myostatin knockout mouse with its bulging muscles dissected on the slide - it looked like "Mighty Mouse" - was unsettling to researchers.

After the completion of the knockout mice experiments, it was hypothesized that high plasma myostatin levels, high plasma HIV viremia and a low rate of muscle protein synthesis were responsible for AIDS muscle wasting. In a study that enrolled HIV-negative subjects, asymptomatic HIV-positive patients, HIV-positive individuals with wasting, and HIV-negative, frail, elderly subjects, plasma myostatin concentration, plasma HIV RNA and muscle protein synthesis rate were measured.

Myostatin levels as well as plasma HIV RNA were found to be highest in the group with AIDS wasting, and the rate of muscle protein synthesis was lowest. There was a direct positive correlation between HIV RNA and myostatin level. The cascading effect of a high viral load augmenting myostatin levels and then inhibiting the rate of muscle protein synthesis may be the reason why AIDS patients develop muscular atrophy. Monitoring circulating myostatin levels may soon be used as a biomarker for muscle wasting in patients with HIV disease.

[advair]

www.drugs.com/increlex.html

[Juggernaut]

I don't think that was a real picture. You might want to check and see if it was photoshopped?

[Harry The Hat]

It's not photoshopped. The pics of the bully whippets with the double-recessive myostatin inhibitor genes have been doing the rounds of the boards - and also of news organizations - for a while now.

This is Wendy.

http://a123.g.akamai.net/f/123/12465/1d/media.canada.com/idl/vitc/20070625/2192-640.jpg

From the 'Times Colonist' newspaper in Canada:

"Wendy was recently part of a genetics study done in the U.S. on mutation in the myostatin gene in whippets, which resemble greyhounds in appearance. The National Institute of Health study reported that whippets with one single defective copy of the gene have increased muscle mass that can enhance racing performance in the breed, known for speeds up to 60 kilometres an hour.

But whippets with two mutated copies of the gene become "double-muscled," like Wendy. It has been seen before in one human, and also in mice, cattle and sheep, says the study."

Can you effect/create myostatin-inhibition? Yes, you can and it was done as early as 1998/9 if I remember correctly with the so-called 'Schwarzenegger mice'.

This article from 2005 shows that athletes are already well aware of the possibilities:

Gene therapy looms as next temptation

By John Powers, Globe Staff | June 5, 2005

It is a tale of mice and men. Or, rather, of men who want to be mice. Once researchers at the University of Pennsylvania produced a ''Schwarzenegger mouse" half a dozen years ago by injecting it with a gene that produced huge muscles, athletes began contacting lab director H. Lee Sweeney, volunteering to become human lab rats.

At a time when elite athletes are injecting themselves with designer steroids and testosterone and human growth hormones and erythropoietin in an effort to gain a winning edge, the next frontier for dopers is gene therapy. ''People are determined to cheat, no matter what the cost," says Dr. Gary Wadler, a New York University medical professor and author of ''Drugs and the Athlete."

Though scientists are hoping to use it to treat diseases like muscular dystrophy, athletes already have seen the potential benefits of an insulin-like growth-factor gene (IGF-1) that can build Mighty Mouse muscles that stay massive for years and keep high-paying careers going indefinitely. While the side effects of gene therapy are unknown and it may be years before the methods are ready for human use, that hasn't kept the athletes from knocking on researchers' doors.

''The sports world doesn't always wait to be safe," says Dr. Theodore Friedmann, who runs the human gene therapy program at the University of California/San Diego.

What works on a mouse may not work on a man, and scientists warn that the methods are still in the experimental stage.

''Things are very different when you go from an animal to a human," says Friedmann, who works with the World Anti-Doping Agency. ''Given the current methodology, anyone who tries it on humans is flirting with real disaster."

Though researchers say it likely will be several years before athletes begin experimenting with gene therapy, the WADA already has added it to its global banned list.

''Any time there's a breakthrough, you'll also see an athlete out there saying, 'If I use this, can I enhance my performance?' " says Wadler. ''To think that's ever going to change is naive."