There has been continuing interest in the case study known widely as the "German super baby." I did a brief post in November linking to the New Scientist article based on the original journal paper (Schuelke, et al., 2004. Myostatin Mutation Associated with Gross Muscle Hypertrophy in a Child. New England Journal of Medicine 350:2682-8), but did not read the original paper and related literature at the time.

As the New Scientist article summarizes, a single point mutation in the gene coding for the protein myostatin causes the condition, which appears to be partial in the boy's mother, who has one mutated allele for the gene, and more dramatic in the case of the boy, with both alleles mutated. Myostatin's function is to inhibit muscle development, and the mutation produces a non-functioning version of the protein. Thus, muscle development continues without inhibition.

Why do we have a protein to inhibit muscle development? Because it is just as important in development to turn processes off as it is to turn them on. If a system in the body is out of proportion to the rest of the body systems, there can be trouble. There always looms the possibility of future health problems, when one's body is out of whack. For example, I found this comment (authenticity unconfirmed, but compelling nonetheless) by "Kangarooistan Man" on a page discussing the condition:

...my father and I both have the "superbaby" mutation. severe myostatin deficiency. My father's bones are near unbreakable and he became locally famous after lifting a minivan.
His strength is comparable to between 3 and 5 normal men and his strength peaked at about the age of 40. His brother Joseph is suspected of having the mutation as well.
Our muscles grow at incredible rates, but don't grow much larger. The muscle fibre packs tightly- so tightly in fact that they tear under their own strength, causing us to suddenly collapse for no apparrent reason with massive muscle tears.
We have body fat of >1% and abnormal muscle definition.
...my father once jokingly held a washing machine in his outstretched arm, obviously considerably more than this 10 lb from the 4 yr old.

I don't know what we are really capable of, but I can tell you from experience that myostatin deficiency is not always a benefit. The constant pain from muscle growth and the inevitable tears that follow are horrendous and it is suspected that the huge muscle mass presses on our blood vessels, forcing blood pressure up and making our hearts less effective.

I'm sure warnings like this will not prevent the next generation of athletes from using whatever "myostatin inhibitor" someone will eventually manage to produce and put on the black market.

Of course, there could be legitimate uses in humans for such a drug, and an obvious discussion has ensued for potential treatment of conditions such as muscular dystrophy. As some researchers in the New Scientist article point out, however, the problems associated with MD are more complicated than just weak muscles, so myostatin inhibition as a treatment is likely still many years away. But, there has been some success in trials using mice with a condition analagous to muscular dystrophy in humans (Benabdallah, B. F., Bouchentouf, M. and Tremblay, J. P., 2005. Improved success of myoblast transplantation in mdx mice by blocking the myostatin signal. Transplantation 79:1696-1702).

What was most intriguing to me about the results of my journal search on "myostatin mutation" was that most papers involve research on livestock. There are breeds of cows with "double muscling" that have this mutation, which is attractive to beef producers. It was in this context that several mutations in the myostatin gene were originally identified in 1997 (McPherron, A. C. and Lee, S. J., 1997. Double muscling in cattle due to mutations in the myostatin gene. Proceedings of the National Academy of Sciences of the United States of America, 94:12457-12461). The discussion involves how the information might be used to manipulate the genetics of other farm animals similarly. The idea that myostatin's function is specifically as muscle growth inhibitor was apparently not introduced until 2002 (Kocamis, H. and Killefer, J., 2002. Myostatin expression and possible functions in animal muscle growth. Domestic Animal Endocrinology 23:447-454). Texel sheep, a "meaty" breed, apparently have a similar mutation as that identified in the human case, a single point mutation of G to A in a myostatin allele (Clop et al., 2006. A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep. Nature Genetics 38:813-818).

As far as I can tell, that sums up the majority of what is known about myostatin. I predict that in a decade or so we will be hearing about a big MI (myostatin inhibitor) ring being broken up, as high school and college kids feel pressure to use it in order to compete, but start collapsing due to muscle tears and circulatory problems. Until the societal and material rewards of a stellar education surpass those of stellar athleticism, the performance enhancement arms race will continue... but that is for another rant, at another time.

Addendum: Apparently there are already a lot of supplements marketed to athletes as "myostatin inhibitors." It is clear from the literature, however, that such a drug has yet to be developed. Fortunately, some sites are honest enough to steer people away from the latest patent medicine.

Here are some pictures, real or not, purporting to show myostatin-deficient animals and humans.

Labels: genetics, humans