Inhibition of signalling via the activin receptor IIB (ActRIIB) is considered a promising therapeutic strategy for Duchenne muscular dystrophy (DMD). A soluble form of activin receptor IIB (ActRIIB fused to the Fc portion of IgG-sActRIIB-Fc) blocks ActRIIB signalling by capturing several ligands of the TGF-beta family of growth factors such as myostatin, which stimulates muscle growth. We treated adult nondystrophic mice (NOD-SCID) and the DMD mouse model mdx with this soluble receptor. Treatment of non-dystrophic mice with rodent specific sActRIIB-Fc strongly stimulated muscle growth and tetanic force, and importantly, there was no increased fatigability. However, treatment of dystrophin deficient mdx mice with sActRIIB-Fc had much lower positive effects on muscle mass and function compared to non-dystrophic mice. Combined treatment with sActRIIB-Fc and AAV-U7-mediated exon skipping to restore dystrophin expression did not increase the effect of sActRIIB-Fc on mdx muscle. We furthermore performed a placebo-controlled and blinded preclinical study on the canine model of DMD and treated 2.5 months old GRMD dogs for 4 months with canine specific sActRIIB-Fc. Results of this preclinical study will be presented.