[HTML][HTML] Fast Skeletal Muscle Troponin Activator tirasemtiv Increases Muscle Function and Performance in the B6SJL-SOD1G93A ALS Mouse Model
DT Hwee, A Kennedy, J Ryans, AJ Russell, Z Jia… - PloS one, 2014 - journals.plos.org
DT Hwee, A Kennedy, J Ryans, AJ Russell, Z Jia, AC Hinken, DJ Morgans, FI Malik…
PloS one, 2014•journals.plos.orgAmyotrophic Lateral Sclerosis (ALS) is a motor neuron disease characterized by progressive
motor neuron loss resulting in muscle atrophy, declining muscle function, and eventual
paralysis. Patients typically die from respiratory failure 3 to 5 years from the onset of
symptoms. Tirasemtiv is a fast skeletal troponin activator that sensitizes the sarcomere to
calcium; this mechanism of action amplifies the response of muscle to neuromuscular input
producing greater force when nerve input is reduced. Here, we demonstrate that a single …
motor neuron loss resulting in muscle atrophy, declining muscle function, and eventual
paralysis. Patients typically die from respiratory failure 3 to 5 years from the onset of
symptoms. Tirasemtiv is a fast skeletal troponin activator that sensitizes the sarcomere to
calcium; this mechanism of action amplifies the response of muscle to neuromuscular input
producing greater force when nerve input is reduced. Here, we demonstrate that a single …
Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease characterized by progressive motor neuron loss resulting in muscle atrophy, declining muscle function, and eventual paralysis. Patients typically die from respiratory failure 3 to 5 years from the onset of symptoms. Tirasemtiv is a fast skeletal troponin activator that sensitizes the sarcomere to calcium; this mechanism of action amplifies the response of muscle to neuromuscular input producing greater force when nerve input is reduced. Here, we demonstrate that a single dose of tirasemtiv significantly increases submaximal isometric force, forelimb grip strength, grid hang time, and rotarod performance in a female transgenic mouse model (B6SJL-SOD1G93A) of ALS with functional deficits. Additionally, diaphragm force and tidal volume are significantly higher in tirasemtiv-treated female B6SJL-SOD1G93A mice. These results support the potential of fast skeletal troponin activators to improve muscle function in neuromuscular diseases.
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