Professors Susan Treves and Francesco Zorzato, Basel University researchers, have recently presented the first potential approach to congenital muscle diseases. Their report was published in a recent article by Science Daily.
Professor Treves stated that she still recalls a child six months old with a congenital muscle disorder. He was barely able to move. Thanks to a heavy schedule of physiotherapy, after several years, the child was able to sit up. This is a major improvement taking into account that there have been no opportunities for recovery to date.
The First Priority
Since there is no cure, the first priority was his survival. Dr. Treves spoke of another boy who had the same mutations as the aforementioned child. This child was not able to survive the disease. The child’s genetic alterations have now become the basis for an approach that Professors Zorzato, Treves, and their team have reported in eLife, a scientific journal.
The mutations affect a gene called RYR1 causing serious consequences to muscle function. A gene alteration was used as a template to create a congenital myopathy mouse model.
Professor Treves said that although the mice did not die, they are smaller, have an impaired muscle system, and are unable to move normally. The team combined two drugs that significantly improved their muscle function as well as their ability to move.
An Excess of Enzymes
The researchers observed that affected patients have excessive amounts of histone deacetylases and DNA methyltransferases enzymes in their skeletal muscles. The density created by the excessive enzymes makes it difficult for the cellular machinery to read and translate the genes into instructions needed to produce protein.
The team, led by Professor Treves, used previously approved inhibitors against the enzymes which created significant improvement for the mice. Their ability to move had improved, yet they were still smaller than the normal mice from the litter. The team announced that they did not witness any serious side effects as a result of the study.
Looking Forward
Professor Treves acknowledges that their approach is only the first step towards the development of an effective treatment. However, she is confident that it is the right step. Their next short-term goal is to test different combinations of new drugs that target the aforementioned enzymes and produce better effects. Professor Treves believes it will be at least two more years before they will be able to begin conducting a phase 1 trial.
Professor Zorzato first isolated the gene that is affected by muscle disorders. The results are promising. They represent ten years that Professors Treves and Zorzato have devoted to the project. They have successfully bridged the gap between isolating the gene and developing a successful therapeutic approach.
