Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy, and impacts almost one million people around the world. It is a genetic disorder that causes the gradual weakening of muscles, and there is no treatment or cure. The disorder is caused by mutations in a gene called SMCHD1, which is critical for halting the production of a toxic protein. Scientists have now found a way to deactivate this toxic protein, which could lead to the development of effective therapeutics for FSHD. The findings have been reported in Nature Communications.
Most FSHD patients have a normal life expectancy, but the diseases has a significant impact on their quality of life because of the severe muscle weakness they experience, noted study co-author Professor Marnie Blewitt, Acting Deputy Director and Laboratory Head at WEHI. "We want to improve their health and quality of life."
As the levels of SMCHD1 get lower, the symptoms of the disease become more serious. The absence or malfunction of SMCHD1 leads to the accumulation of a toxic protein that ruins muscle function, added Blewitt, whose team has been searching for ways to boost SMCHD1 production for many years. In pre-clinical models, an increase in SMCHD1 function lowered the production of toxic proteins.
Normally, SMCHD1 collects genes that it usually silences into specific parts of a cell's nucleus. This research has also revealed that the gene gathering function of SMCHD1 and its silencing abilities are totally separate, noted first study author Andres Tapia del Fierro, a Ph.D. student in the Blewitt lab.
"This was an unexpected, yet crucial finding, that really took the team by surprise," Tapia del Fierro said. "Without this fundamental discovery, we would still think these two functions are linked. This would have seen us dedicate years towards trying to find new ways to boost SMCHD1 function, by boosting its ability to gather genes, which we now know won't work."
Now, investigators are looking for other SMCHD1 functions that might also enhance its ability to silence genes. While they have not yet found the way to increase the silencing ability of SMCHD1, they have now eliminated a possibility, noted Tapia del Fierro
"The next step is to figure out how to translate these milestone findings to benefit humans, by determining the best way to boost SMCHD1 and its silencing powers to hopefully find a cure for FSHD."
Sources: Walter and Eliza Hall Institute (WEHI), Nature Communications