Mavacamten for 4 weeks does not improve the condition of mice models of nebulin-related nemalin myopathy

In muscle fibers from individuals with nebulin-related nemaline myopathy (NEB-NM) and in NEB-NM mouse models, the proportion of myosin in the disordered relaxed state and ATPmolécule représentant la principale forme d’énergie immédiatement utilisable par la cellule pour son fonctionnement. consumption are abnormally increased, accompanied by a reshuffling of the energy proteome of these cells.

• Mavacamten, which reduces the amount of myosin in the disordered relaxed state in hypertrophic cardiomyopathy, normalizes ATP consumption in skeletal muscle fibers from patients with NEB-NM.
• Administered for four weeks to NebKO mice, it did not improve the clinical and histological phenotype of the mice (in contrast to what was observed in Laing myopathy).
• While it caused changes in the proteome, it did not alter the energy proteome of the mice.

Myosin ATPase inhibition fails to rescue the metabolically dysregulated proteome of nebulin-deficient muscle. Laitila J, Seaborne RAE, Ranu N et al. J Physiol. 2024 Aug 31.