A team from Strasbourg, supported by the AFM-Telethon, has studied the repositioning of tamoxifen in centronuclear myopathy (CNM), a drug which has already shown its efficacy in the animal model of myotubular myopathy or Duchenne muscular dystrophy.
The investigators studied the effects of five weeks of tamoxifen administration in two three-week-old mouse models: one of BIN1-related centronuclear myopathy (CNM-BIN1) and one of DNM2-related CNM (CNM-DNM2).
Compared to untreated mice, those taking tamoxifen showed :
- an improvement in muscle strength in CNM-BIN1 and CNM-DNM2 mice, from day 7 of treatment;
- better overall motor performance in CNM-DNM2 mice, and a significantly higher capacity for submaximal effort, with an increase of almost 80% in muscle force production;
- a complete disappearance of histological abnormalities (protein aggregates, mitochondrial malposition, etc.) in CNM-BIN1 mice, but not in CNM-DNM2 mice;
- a normalisation of DNM2 protein levels in CNM-DNM2 and CNM-BIN1 mice by regulation of the proteasome, but no impact on the high levels of BIN1.
However, in both models, tamoxifen does not reduce muscle atrophy or the abnormally high DNM2 levels in the patient cell models.
The improvement in myopathy in mice with established disease demonstrates the potential therapeutic utility of tamoxifen in both early and late onset centronuclear myopathies.
A phase 1/2 clinical trial of tamoxifen in patients with myotubular myopathy is ongoing.
