The necessity for skeletal muscle contractile assays to assess treatment efficacy in DMD

Abstract

Body movement relies on skeletal muscles generating power to move limbs effectively. Power is defined as force multiplied by velocity: a muscle produces force at a specific velocity (the speed of muscle shortening) and this results in power. In diseases like Duchenne Muscular Dystrophy (DMD), the absence of dystrophin weakens muscles and impairs their shortening velocity, leading to decreased power and consequently, impaired movement. Additionally, the diaphragm and heart muscles are also affected in DMD, causing difficulty breathing and impaired cardiac function. Compromised cardiorespiratory function can ultimately lead to death. Given the complex etiology of DMD and the essential role of power in all affected muscles, it is crucial to assess potential treatments for their effectiveness in improving muscle function. This review focuses on fundamental physiological assays used to evaluate muscle function in skeletal and diaphragm muscles. Common assays include force-frequency, force-velocity, power, and eccentric protocols, which are conducted ex vivo, in situ, and in vivo in small rodents (such as mice and rats) and larger intermediate animal models such as the Golden Retriever Muscular Dystrophy dog. Existing data support the use of skeletal muscle contractile assays as objective tools for assessing the efficacy of treatments.

Keywords

Dystrophic muscle / contraction / ex vivo / in situ / in vivo

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