RESUMO
INTRODUCTION: Tirasemtiv is a novel small molecule activator of the fast skeletal muscle troponin complex that produces sensitization of the sarcomere to calcium. Tirasemtiv is currently in Phase II clinical trials for neuromuscular disease. METHODS: We conducted a blinded, randomized, placebo-controlled preclinical study of the effect of tirasemtiv on forearm grip strength, endurance, respiratory physiology, and muscle pathology in adequate sample sizes of the Lama2(dy-2J) mouse model of congenital muscular dystrophy. RESULTS: Mice receiving a high dose of tirasemtiv had significantly higher muscle fiber cross-sectional area and respiratory response to CO2 stimulation at 16 weeks than mice on low dose or placebo. There were no changes in muscle pathology, serum creatine kinase, strength, endurance, or respiration following long-term treatment. CONCLUSIONS: We conclude that tirasemtiv influences the structure of the skeletal muscle fiber in this model of muscular dystrophy but does not impact muscle function, as evaluated in this study.