A French research team has found that reducing levels of a protein called dynamin 2 has potential as a strategy to treat myotubular myopathy (MTM), a form of centronuclear myopathy (CNM), and that it could have implications for other nerve and muscle disorders as well.
The findings shed new light on the biochemical underpinnings of MTM, a disease in which the myotubularin protein is deficient, and provide a new lead for therapeutic development.
Current experimental treatments in development for MTM are based on injecting the myotubularin protein or genes for this protein, both of which have received MDA support. The strategy suggested by the new findings could be an alternative or an addition to therapies that are based on increasing myotubularin protein levels.
Belinda Cowling at the Institute of Genetics and Molecular and Cellular Biology (IGBMC) in Illkirch, France, and colleagues, conducting experiments in mice with a disease resembling MTM, published the new dynamin 2 findings March 3, 2014, in the Journal of Clinical Investigation.
An editorial by Alexis Demonbreun and Elizabeth McNally, both at the University of Chicago, accompanies the paper. McNally has received MDA support to study the molecular basis of various muscle disorders.
Myotubularin may keep dynamin 2 in check
The investigators say they think myotubularin normally acts as a check on dynamin 2, perhaps keeping it from lasting too long in the body, particularly in muscle fibers. When myotubularin is deficient, as it is in MTM patients, dynamin 2 appears to last longer than usual, causing damage.
The researchers found that reducing the level of the dynamin 2 protein in myotubularin-deficient mice increased life span and improved motor function.
The strategy used by the scientists to reduce dynamin 2 levels in the mice was a type of genetic engineering not readily translatable to treatment for human patients. However, reduction of dynamin 2 or interference with its function by other methods could potentially be developed for human use.
Other diseases could benefit, too
Interestingly, mutations in the gene for dynamin 2 cause a form of CNM unrelated to myotubularin deficiency and also cause the 2M form of the peripheral nerve disorder known as Charcot-Marie-Tooth disease (CMT).
Dialing down dynamin 2 levels could have implications for these disorders and possibly even other neuromuscular diseases.
In the editorial accompanying the March 3 paper, Demonbreun and McNally say that if elevated dynamin 2 levels are found in other disorders, then "targeting dynamin 2 becomes a common therapeutic strategy for a wider range of muscle disease."