Myotubular myopathies (MTM) are rare diseases which cause severe muscle weakness and particularly target the muscles which are essential to maintain life i.e. to breathe and eat. Other organs such as the liver are also affected. The most severe form of the disease is present from birth and affected babies struggle to survive.
In most forms of MTM, the protein myotubularin is missing. This protein is thought to have a role in controlling muscle growth i.e. how big and strong our muscles become. It may also be important for maintaining muscle function throughout adulthood. However, it is currently unclear how the loss of this protein causes MTM.
The Myotubular Trust has now funded two research projects to address this important question from two different angles.
The first project, which will be run by Dr Richard Piercy, a Vet at The Royal Veterinary College, will use a naturally occurring Labrador dog model for the disease, to try and understand what aspect of muscle function has stopped working properly in these muscle diseases. To do this, he is going to take muscle cells from both a healthy and a MTM-affected dog, grow them in the laboratory and compare these cells for differences in cell pathology, such as cell size and shape. He will also compare the muscle cells for how well they work when asked to contract. This will give an indication of the strength of the muscle.
The second project, which will be run by Dr Anna Buj-Bello at INSERM, a French laboratory, will use mouse models for the disease. She will try a variety of therapeutic ‘rescue’ approaches such as gene therapy and drug administration. Her mice models lack myotubularin either from just muscle or from all body tissues. She will then add back myotubularin or a drug and monitor all of the body organs over time for health improvements. She will treat mice both prior to and subsequent to the development of the clinical symptoms of MTM. Therefore these experiments will not only tell us whether this treatment will be suitable to alleviate the clinical symptoms of the disease, but also whether it could stop the development of the disease from the outset. The research output from both of these projects is likely to suggest therapeutic strategies to treat MTM patients of all ages.