Myotubular myopathy is a severely genetic disease leading to muscular paralysis and even results in death at a young age, however researchers may have found a way to fight it.
The University of Geneva (UNIGE), Switzerland, working in assocation with the University of Strasbourg, France, have identified a molecule that not only vastly reduces the progression of the disease but also boosts life expectancy. Since the molecule tamoxifen, is already used to treat breast cancer, the researchers anticipate to soon schedule a clinical trial so that patients can be given the medication and help battle muscular paralysis.
What do you know about muscular paralysis?
Myotubular myopathy is a severe genetic disease that weakens all the skeletal muscles from birth. 90% of affected babies do not live to two years of age.
Myotubular myopathy is caused by a lack of myotubularin, which is an enzyme that transforms the lipidic messengers. Without this, the protein known as dynamin 2 accumulates and causes muscle atrophy. In the search for a cure, one of the avenues explored by several groups, including UNIGE’s colleagues in Strasbourg, is to target dynamin 2, which is modulated by tamoxifen.
Leonardo Scapozza, professor at the School of Pharmaceutical Sciences at UNIGE’s Faculty of Science explains: “The disease affects the X chromosome in one in 50,000 male infants.” Therefore, only boys are struck by myotubular myopathy, since the second X chromosome in girls generally compensates for the possible mutation of the first.
The multipurpose molecule, tamoxifen
The researchers focused more on tamoxifen, which has been used for many years to treat breast cancer. The molecule was also of particular interest to the study of muscular paralysis as it has several interesting properties for protecting muscle fibres such as being an antioxidant, anti-fibrotic and also protects the mitochondria.
“In a previous study, we used tamoxifen against Duchenne muscular dystrophy, which is also an inherited muscular disease that affects one in 3,500 boys, where the life expectancy is 30 years.” Explains Elinam Gayi, a PhD student in UNIGE’s School of Pharmaceutical Sciences.
Details of the study
The scientists began the treatment on the subjects when paralysis of the hindlegs occurred at about three weeks. However, they have highlighted that administering the drug earlier might be more efficacious against muscle weakness and muscular paralysis.
Moreover, from the study, the progress of the muscular paralysis was slowed down massively or even completely stopped. Muscular strength was tripled, and it was possible to recover 60% of the muscular deficit between a healthy mouse and a sick mouse.
“In parallel to our study, a team from the Children’s Hospital of Toronto tested the drug on even younger mice, and the disease did not develop,” says Olivier Dorchies, a researcher in the School of Pharmaceutical Sciences.
“The problem is that in humans, myotubular myopathy starts during foetal development, so it’s hard to know whether the total absence of paralysis might be achieved if this molecule is given after birth.”
Will a clinical trial be set up to tackle muscular paralysis?
Elinam concludes: “Since tamoxifen is already authorised for use in humans, and a clinical trial is underway for Duchenne muscular dystrophy, we’re hopeful that a clinical trial will come on line within a couple of years.”
The researchers aim to continue the exploration of tamoxifen for treating genetic muscle diseases and will try to combine it with other authorised molecules. The ultimate goal is to find treatments that can be put on the market quickly and tackle debilitating conditions such as muscular paralysis.
