Administration study of black market ACE-031 (Ramatercept)

Code: 21C11CR

Chapter S4 of WADA’s Prohibited List 2021 (“Hormone and Metabolic Modulators”) lists ACE-031 under sub-chapter 3 (“Agents preventing activing receptor IIB activation, Activin receptor IIB competitors – Decoy activing receptors”) as prohibited substance. ACE-031 (Ramatercept) is a soluble fusion protein, which blocks activin receptor type II B (ActRIIB) ligands including myostatin. So far, no approved ACE-031 pharmaceuticals are available. On the other hand, ACE-031 is sold on the black market. However, the administration of black market ACE-031 to human test persons will be ethically not justifiable. For that reason we plan a study with rats. Page 2/7 The test animals will receive black market ACE-031 at a dosage, which can be clearly detected in serum (10 mg/kg BW). After 24, 48 and 168 hours, serum and urine will be collected and tested for ACE-031 by electrophoresis and Western blotting. In addition, the metabolism of black market ACE-031 will be investigated in human microsomes as the metabolites in rat may be different from those in humans. The study will help to clarify (1) how long black market ACE-031 is detectable in blood, (2) if it can also be observed in urine, and (3) if metabolites are different in rats and humans. We have already developed a method for the detection of black market ACE-031 after electrophoretic separation and Western blotting (SDS-, SAR-PAGE).