Myotubular myopathy
RSS feedMyotubular myopathy: are cardiac compensatory mechanisms at work?
The team at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) in Strasbourg has explored the non-neuromuscular effects of myotubular myopathy in the Mtm1-/y mouse model: no functional or morphological abnormalities were found in the liver; alongside the disturbances in muscle development, inflammation, cell adhesion and oxidative phosphorylation found in skeletal muscle, … [Read more]
Overview of neuromuscular diseases
After a brief reminder of the structure of the motor unit and the various modes of inheritance, this document provides short descriptions of the neuromuscular diseases that are part of our scope at AFM-Téléthon, as well as how to manage and treat them. For each group of diseases, as well as in the motor unit … [Read more]
Physical training pays off in myotubular myopathy
A 23-year-old Dutch man with a moderate form of X-linked mytotubular myopathy describes his experience of physical training and its benefits in a publication: inclusion in the Nathis-CNM natural history study in 2015 and the prospect of entering the Unite-CNM clinical trial triggered his decision to improve his fitness and stick to it; the introduction … [Read more]
ASPIRO trial: muscle lesions regress less quickly and less completely than in dogs
Muscle biopsies were taken before and after gene therapy in 10 children with myotubular myopathy participating in the ASPIRO trial. At 24 weeks after treatment, organelle localization was greatly improved, with no increase in myofibril size in most cases. On biopsy at 48 weeks post-treatment, the increase in myofibril size became statistically significant. However, the … [Read more]
Myotubular myopathy: the encouraging lead of PI3KC2β inactivation
In the November 2023 issue of Cahiers de myologie, the team from the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), repeat in French the results they obtained and published in English in May 2023 in the journal JCI Insight: total selective inactivation of PI3KC2β kinase activity prevents muscle atrophy and weakness, as … [Read more]
Myotubular muscular dystrophy: trial results show efficacy on respiratory and motor function, but challenges remain
Yesterday, The Lancet Neurology published the clinical results of a gene therapy trial conducted by Astellas Gene Therapies, using a drug candidate developed at Genethon, in 24 children suffering from myotubular myopathy, a very severe muscle disease. This international trial, which is taking place in 6 investigating centres around the world, including I-Motion, the Institut … [Read more]
Myotubular myopathy: in zebrafish, hepato-biliary damage is due to loss of function of myotubularin
A North American team has characterised the liver phenotype of a zebrafish model of myotubular myopathy. The loss-of-function anomaly in mtm1 results in impaired bile flow and structural anomalies in the bile canaliculi, with inadequate endosomal trafficking of bile transporters. Hepatocyte re-expression of myotubularin 1 is sufficient to at least partially restore these abnormalities. Two … [Read more]
Myotubular myopathy: valproic acid improves mouse models and leads to the identification of a specific epigenetic signature
Screening of 1280 molecules on zebrafish models of X-linked myotubular myopathy (XLMTM) showed that histone deacetylase (HDAC) inhibitors such as valproic acid or trichostatin A improved their swimming speed in a dose-dependent manner. Similarly, Mtm1-/y model mice had their survival prolonged and their motor capacity (suspension test) improved by these molecules, and this to a … [Read more]
The INCEPTUS study confirms the frequency of liver damage in X-linked myotubular myopathy
The international INCEPTUS study, a natural history study prior to the ASPIRO gene therapy trial to which I-Motion (Hôpital Armand trousseau, Paris) contributed, involved 34 children under 4 years of age with X-linked myotubular myopathy on respiratory support. During a median follow-up of 13 months (from 5 months to more than 2.5 years), there were … [Read more]
Liver damage in myotubular myopathy
Hepatobiliary involvement, such as gallstones or peliosis hepatis, has been reported in several cases of myotubular myopathy since the 1990s. It was found in 7% of participants in the Recensus study or the natural history study NatHis-MTM. With the death from severe hepatic insufficiency of three participants in the ASPIRO trial receiving the highest dose … [Read more]
