Myostatin and myostatin inhibitors
Myostatin Inhibitors: New Protein Therapeutics in Doping Analysis
The growth of human skeletal muscle is regulated by the cytokine myostatin [1]. This protein, which belongs to the transforming growth factor-beta (TGF-β) family, binds to type-2 activin receptors on its target cells, thereby triggering signaling pathways that ultimately result in the inhibition of muscle growth. Drugs that neutralize the effects of myostatin are therefore of great interest for the treatment of diseases associated with muscle wasting. However, elite athletes could also use such myostatin inhibitors to artificially increase muscle mass. For this reason, the use of these substances has been banned for quite some time in both training and competition.
Currently, numerous different myostatin inhibitors are in clinical development [2, 3]. While anti-myostatin antibodies and a modified variant of the body’s own myostatin propeptide specifically target only free-circulating myostatin, there are also strategies to simultaneously neutralize multiple ligands of the activin type-2 receptors. For this purpose, both soluble forms of the Activin type-2 receptors, for example in the form of Fc fusion proteins, and anti-ActRII antibodies can be used.
(June 1, 2018 Katja Walpurgis)
Significance as a Doping Agent
This type of manipulation—i.e., the use of substances to inhibit myostatin—has been banned by the World Anti-Doping Agency (WADA) since January 1, 2008, under Group S4 of hormone antagonists and modulators. Since 2013, Group S4 has been designated as “Hormone and Metabolic Modulators.”
Excerpt from the English text of the 2018 WADA Prohibited List:
The following hormone and metabolic modulators are prohibited:
...
4. Agents modifying myostatin function(s) including, but not limited to: myostatin inhibitors
....
References
[1] A. C. McPherron et al. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997, 387, 83-90
[2] M. N. Fedoruk et al. Myostatin inhibition: a potential performance enhancement strategy? Scand J Med Sci Sports. 2008, 18, 123-131.
[3] R. C. Smith et al. Myostatin inhibitors as therapies for muscle wasting associated with cancer and other disorders. Curr Opin Support Palliat Care. 2013, 7, 352-360.
Detection of Bimagrumab
Detection of Bimagrumab (a myostatin inhibitor)