Following contacts established long ago between AFM and Russian specialists, in particular between S. Braun and A. Baranov, a round-table meeting on neuro-muscular disorders was held in Paris from 9-11 April. The organizers, the French Association Française contre les Myopathies (AFM), the Institut de Myologie and TREAT-NMD had invited representatives from clinical and research centres and patient organisations from Moscow, St Petersburg and Minsk. Representatives from ENMC and Acies also participated to the round-table discussions.

An international team of researchers has taken a big step toward developing a cure for Duchenne muscular dystrophy by successfully treating dogs with naturally occurring canine X-linked muscular dystrophy, a disease which is genetically homologous to the Duchenne muscular dystrophy that affects 1 in 3,500 boys. Exon skipping was employed to restore partial function to the dystrophin gene that is involved in Duchenne. Unlike traditional gene therapy, which attempts to replace a mutated gene with a functional copy, exon skipping is a strategy that masks the error-containing exons in such a way that they're skipped over, and the remaining, correct instructions surrounding the region are spliced together. The newly spliced instructions allow for production of a nearly normal, functional protein that's free of genetic errors. Three dystrophin-deficient dogs were each given intravenous injections of a cocktail of exon-skipping compounds either weekly or every other week. All three showed new dystrophin production in all examined muscles, although the degree of production varied. The average dystrophin protein production level was greatest in the dog given seven weekly doses of 200 milligrams per kilogram of the exon-skipping cocktail, causing dystrophin levels to rise from zero to 26 percent of normal. Functional improvement of the treated dogs compared to untreated littermates was assessed by a 15-minute timed running test and by a combined functional score. The untreated littermates became slower over the treatment time, whereas all treated dogs ran faster after treatment. Furthermore, marked improvements in the microscopic appearance of the muscle tissue and other measures of muscle health were observed. This is the first successful application of “multiple exon-skipping” to curb the devastating effects of Duchenne muscular dystrophy in an animal larger than a mouse. However, further studies are required before human application can be considered because DMD sufferers often have different genetic mutations.

A team of American researchers, including 2007 Nobel Prize winner Mario R. Capecchi, have created a “switch” that allows mutations to be turned on in muscle stem cells to monitor muscle regeneration in a living mammal. For humans, this work could lead to a genetic switch, or drug, that allows people to grow new muscle cells to replace those that are damaged, worn out, or not working for other reasons (e.g., muscular dystrophy). In addition, this same discovery also gives researchers a new tool for the study of difficult-to-treat muscle cancers. The discovery was revealed by breeding mice with a specific gene, called Cre which, when activated, can trigger mutations in muscle stem cells. This Cre trigger is restricted to muscle stem cells and requires a special drug for it to be activated. In one part of the study, using fluorescent techniques, the researchers were able to visualize stem cells and their derivatives in order to identify exactly where muscle tissue was being made. Until now it has not been possible to tag muscle stem cells and observe their division with this level of specificity. In another part of the study, the scientists were able to activate tumor-causing mutations in muscle stem cells, providing valuable insights into the origins of muscle tumors, which have been previously elusive. It is hoped that these new genetically-engineered mouse models will help scientists and clinicians better understand how to make muscle stem cells regenerate muscle tissue. Determining how to selectively turn on this muscle regeneration switch in mature mice could have implications in the near future not only for muscular dystrophy patients and muscle-related injuries, but also for aging adults.