Small molecule drugs to improve sarcomere function in those with acquired and inherited myopathies

Wout J. Claassen, Rianne J. Baelde, Ricardo A. Galli, Josine M. de Winter, Coen A.C. Ottenheijm

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Muscle weakness is a hallmark of inherited or acquired myopathies. It is a major cause of functional impairment and can advance to life-threatening respiratory insufficiency. During the past decade, several small-molecule drugs that improve the contractility of skeletal muscle fibers have been developed. In this review, we provide an overview of the available literature and the mechanisms of action of small-molecule drugs that modulate the contractility of sarcomeres, the smallest contractile units in striated muscle, by acting on myosin and troponin. We also discuss their use in the treatment of skeletal myopathies. The first of three classes of drugs discussed here increase contractility by decreasing the dissociation rate of calcium from troponin and thereby sensitizing the muscle to calcium. The second two classes of drugs directly act on myosin and stimulate or inhibit the kinetics of myosin-actin interactions, which may be useful in patients with muscle weakness or stiffness.

Original languageEnglish (US)
Pages (from-to)C60-C68
JournalAmerican Journal of Physiology - Cell Physiology
Volume325
Issue number1
DOIs
StatePublished - Jul 2023
Externally publishedYes

Keywords

  • muscle disease
  • muscle physiology

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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