Myotubular myopathy is a rare genetic disease caused by mutations in the MTM1 gene. A study carried out in animals by researchers from Inserm, CNRS and the University of Strasbourg at the IGBMC, in collaboration with American teams, has shed light on the underlying mechanisms of this disease. Published in the journal Science, these studies suggest that vitamin K supplementation could improve certain symptoms of the disease, opening up new therapeutic prospects.
Myotubular myopathy, also known as X-linked centronuclear myopathy, is a rare and severe genetic disease affecting newborns and children. It affects around one child in 50,000. Linked to a mutation in the MTM1 gene on the X chromosome, it manifests itself as an alteration in the size and shape of muscle fibers. The main symptoms are generalized muscle weakness and respiratory distress.
There is currently no therapy, and our knowledge of myotubular myopathy is still patchy. Thanks to a collaboration between the teams of Jocelyn Laporte, Inserm Research Director at IGBMC, and Llyod Trotman at Cold Spring Harbor (USA), the mechanisms of this disease have nevertheless been clarified. In particular, the scientists demonstrated that pro-oxidant vitamin supplementation could improve the symptoms of the disease in an animal model.
The effects of vitamin K supplementation
In myotubular myopathy, the loss of the MTM1 protein, linked to mutation of the gene of the same name, results in a surplus of a lipid called PI3P. In this context, scientists are interested in an enzyme, the VPS34 kinase, which could be one of the keys to understanding this mechanism. Indeed, we know that VPS34 produces this lipid and opposes the action of the MTM1 protein. It could therefore be a lever to be exploited in an attempt to act on the disease.
In this study, the scientists began by showing that the action of VPS34 can be blocked by an oxidation mechanism. With this in mind, they set out to determine whether this "blockage" could have an effect in correcting myotubular myopathy.
To do so, they focused on a well-known vitamin, vitamin K, which is naturally present in green leafy vegetables (such as kale, spinach and collards), soybean oil and rapeseed oil. In fact, this vitamin has oxidizing properties.
Scientists therefore added a vitamin K precursor to the diet of myotubular myopathy mouse models. They showed that this vitamin supplementation significantly improved the life expectancy of these mice, as well as their muscle mass and organization, and consequently their motor function.
"These encouraging animal results confirm our belief that acting on VPS34 kinase, via vitamin K supplementation, could be a promising way of improving the symptoms of the disease," explains Jocelyn Laporte.
These results now need to be validated in larger studies and clinical trials. Ultimately, they could lead to the recommendation of vitamin K supplementation for patients with myotubular myopathy, in the hope in particular of improving their motor skills and autonomy.