![]() The inotropic effects of tirasemtiv were present in locomotor muscles and, albeit to a lesser extent, in respiratory muscles, and they persisted during chronic treatment, an important finding as respiratory failure is the main cause of death in patients with congenital myopathy. This resulted in a reduced energetic cost of force generation, which increases the force production during a fatigue protocol. In Acta1 H40Y mice, treatment with tirasemtiv increased the force response of muscles to submaximal stimulation frequencies. We tested the ability of tirasemtiv, a fast skeletal troponin activator that targets the thin filament, to augment muscle force-both in vivo and in vitro-in a nemaline myopathy mouse model with a mutation (H40Y) in Acta1. ![]() To date, no specific therapy is available to treat muscle weakness in nemaline myopathy. Nemaline myopathy, a disease of the actin-based thin filament, is one of the most frequent congenital myopathies.
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