Myotubular myopathy is an X-linked genetic disease that affects 1 in 50,000 newborn boys. This rare genetic disease causes muscle paralysis from birth and leads to death before the age of 2 years. Although no treatment currently exists, researchers therefore this team from the University of Geneva (UNIGE) is working to find a treatment. In collaboration with colleagues from the University of Strasbourg, Swiss researchers have identified a molecule which not only considerably reduces the progression of the disease, but also increases the life expectancy of animal models of the disease by a factor of 7. The well-known molecule, tamoxifen, used in the treatment of breast cancer is already considered and under clinical trial for the treatment of another myopathy,
Tamoxifen, a versatile molecule with interesting properties for the protection of muscle fibers: antioxidant, antifibrotic and protective of the mitochondria, tamoxifen is already being studied in the treatment of Duchenne muscular dystrophy. The first results are promising and a clinical trial is underway. This is why the scientists hypothesized that the molecule could also be effective in combating myotubular myopathy. Myotubular myopathy is caused by a lack of myotubularin, an enzyme which transforms lipid messengers and this deficiency induces an accumulation of a protein, dynamin 2 which will cause muscle atrophy. It “happens” that tamoxifen modulates dynamin 2 levels.
Evidence in the model mouse: The researchers administered 3 doses to 3 groups of these model mice (0.03 milligrams per kilogram, 0.3 milligrams per kilogram and 3 milligrams per kilogram), the highest dose corresponding to that used to treat breast cancer in women.
- While an untreated sick mouse lives an average of 45 days,
- the lower dose increases survival at 80 days,
- the intermediate dose at 120 days,
- the highest dose at 290 days, 7 times higher than the control group.
- With the highest dose,
- some mice even survived more than 400 days,
- muscle strength is tripled and it appears possible to recover 60% of the muscle deficit between a healthy mouse and a sick mouse.
Alongside this study , a team from Toronto Children's Hospital tested the drug on even younger mice and the disease did not develop, the researchers add. "The problem is that in humans, myotubular myopathy begins during fetal development, so it is unclear whether complete freedom from paralysis could be achieved if treatment is started after birth."
A clinical trial is planned in the next two years and the UNIGE team will continue its research on the multiple uses of tamoxifen in the treatment of genetic muscle diseases.The objective is to develop treatments that can be brought to market quickly.