Saturday, August 20, 2011

Doping 2.0 - Myostatin Blocker. We are Finally There! Orally(!) Administered Recombinant Yeast Increases Body Weight and Muscle Composition in Rodent Model.

Image 1: "Wendy" myostatin negative dog
and 7 months old baby of a 24-year old
female former athlete with a family
history of "particular" strength
(image "baby" from Schuelke. 2004)
You have seen those images of myostatin-negative bulls, mice and dogs. Those ugly overmuscled creatures, who cannot even carry the weight of their own musculature. Notwithstanding, you were fascinated by the idea that myostatin blockers, i.e. drugs that inhibit the growth and differentiation factor 8 (GDF8), would turn you into lean, mean mass-monster, but the only results you could find in reliable source were disappointing? Well, you may then get even more excited, when the reliable source your are just studying is telling you that "we are finally there"! Scientists from the Shaan’xi Key Laboratory of Molecular Biology for Agriculture at the Northwest A&F University in Shaan’xi, China have found a way to selectively increase muscle weight in mice by oral administration of a whole recombinant yeast Saccharomyces cerevisiae vaccine (Zhang. 2011).

Before the yeast was administered to the mice at a weekly dose of 120,000,000 yeast cells for 5 weeks, Zhang et al. had cultured the yeast with copper sulfate for 10h to induce the expression of myostatin and ovo-myostatin proteins.
Figure 1: Increases in body weight of 5-week old Kunming mice after 5 weeks of oral or intravenous treatment with recombinant yeast cells (calculated based on data from Zhang. 2011).
As the data in figure 1 goes to show, the oral "immunization" procedure turned out to be more effective than the scientists had even hoped for. Still, vaccination by injection was 7% and 9% more growth promoting for the myostatin (MSTN) and ovo-myostatin (Ovo-MSTN) yeast, respectively.
Figure 2: Additional muscle gain measured in forelimb, hindlimb muscles, as well as triceps brachii and biceps femoris compared to control in 5-week old Kunming mice after 5 weeks of oral or intravenous treatment with recombinant myostatin or ova-myostatin yeast cells (calculated based on data from Zhang. 2011).
In view of both agricultural applications, as well as legal and illegal performance enhancement in recreational and professional athletes, the most important finding of the study yet turns out to be a null-finding: Null, that is the number of pathological change the scientists observed in the course of the study - no abnormal organ growth, muscle weakness and all the other ailments myostatin-null mice, bulls, dogs and whatever poor animals scientists have hitherto genetically modified, usually suffer from:
In  this  study, immunized mice in all groups were found generally healthy looking and  no  significant  damage  in  any  internal  organs. [If one also takes into account the report on the "myostatin baby" by Schuelke et al. (Schuelke. 2004)] these findings suggest  that  immuomodulation  of  myostatin  is  safe in  both  laboratory  animals  and  human.

Image 2: While the mice did gain significant
amounts of weight (esp. muscle) they are
completely healthy and do by no means
look as bulky as genetically modified dogs,
bulls and co. (image from Zhang. 2011).
If you look at the mice in image 2, it is in fact hard to tell, which of the mice received the control and which the myostatin yeast and that despite the fact, that - assuming similar effects in adolescent human beings - the average sleeve size of humans who have been immunized with this yeast would increase from ca. 32cm to ca. 43cm! That being said, it is unlikely that the "immunization", which has your body produce antibodies against myostatin and thus blocks the inhibitory effect of the TGF beta protein on muscle growth, will produce such profound results in adults, whose bodies obviously are not primed to growth in the way the bodies of children or adolescents are... but hey, there are enough aspiring young athletes in the Chinese Olympic Team to see preliminary results in 2012 (hoops, I think this was not 100% politically correct ;o)