Fast Skeletal Muscle Troponin Activator tirasemtiv Increases Muscle Function and Performance in the B6SJL-SOD1G93A ALS Mouse Model

摘要: Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease characterized by progressive loss resulting in muscle atrophy, declining function, and eventual paralysis. Patients typically die from respiratory failure 3 to 5 years the onset of symptoms. Tirasemtiv fast skeletal troponin activator that sensitizes sarcomere calcium; this mechanism action amplifies response neuromuscular input producing greater force when nerve reduced. Here, we demonstrate single dose tirasemtiv significantly increases submaximal isometric force, forelimb grip strength, grid hang time, rotarod performance female transgenic mouse model (B6SJL-SOD1G93A) ALS with functional deficits. Additionally, diaphragm tidal volume are higher tirasemtiv-treated B6SJL-SOD1G93A mice. These results support potential activators improve function diseases.