Mavacamten facilitates myosin head ON-to-OFF transitions and shortens thin filament length in relaxed mouse skeletal muscle.

ABSTRACT: The first-in-its-class cardiac drug mavacamten shifts myosin heads towards a structurally inactive position where they lay along the helical tracks of the thick filament. However, mavacamten is not completely specific to cardiac myosin and can also affect skeletal muscle myosin, an important consideration since mavacamten is administered orally and so will also be present in skeletal tissue. Indeed, emerging clinical reports indicate mavacamten-induced generalized skeletal myopathy in elderly patients. These findings raise important safety considerations for vulnerable populations, while also highlighting the drug's potential as a novel basic research tool to probe thick filament regulation and myosin head availability in skeletal muscle mechanics experiments. Using small-angle X-ray diffr

SUBMITTER: Kuehn MN 

PROVIDER: S-EPMC12558621 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature