TIRASEMTIV Troponin Activator Treatment of Amyotrophic Lateral Sclerosis

The identification of new targets for specific and effective therapies poses new challenges for the treatment of several muscle diseases causing weakness (e.g., amyotrophic lateral sclerosis [ALS]). Recent advances have pointed out that sarcomeres may represent potentially useful pharmacological targets. As a result, screening studies for activators of the troponin-tropomyosin complex have resulted in the identification and optimization of a selective fast skeletal troponin activator, tirasemtiv (CK-2017357), which sensitizes fast muscle fibers to calcium. The action of this drug causes an increase in muscle force development at submaximal activation. In vitro and in vivo experiments have further supported the proposed mechanism of action of tirasemtiv. Encouragingly, phase I and phase II trials in ALS patients have shown a favorable safety profile and efficacy in functional improvements of skeletal muscle performance and in reducing fatigability. For this reason, the target enhancement of contractility derived from administration of tirasemtiv may be capitalized upon for the treatment of several variable pathologies, from cardiac and skeletal muscle pathologies to other neuromuscular disorders and claudication.