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Fast skeletal muscle troponin activator in the dy2J muscular dystrophy model
Author(s) -
Miciak Jessica J.,
Warsing Leigh C.,
Tibbs Maria E.,
JASPER Jeffrey R.,
Jampel Sarah B.,
Malik Fady I.,
Tankersley Clarke,
Wagner Kathryn R.
Publication year - 2013
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.23848
Subject(s) - skeletal muscle , medicine , duchenne muscular dystrophy , troponin , muscular dystrophy , sarcomere , creatine kinase , neuromuscular disease , troponin t , troponin i , cardiology , endocrinology , myocyte , disease , myocardial infarction
: 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 CO 2 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. Muscle Nerve , 48: 279–285, 2013