New Targets Found for Drug Therapy of Facioscapulohumeral Muscular Dystrophy
One of the most common forms of muscular dystrophy is Facioscapulohumeral Muscular Dystrophy (FSHD). FSHD mainly affects the upper part of the body, causing muscular weakness in the facial muscles, shoulders, and arms.
FSHD was classified as a separate form of muscular dystrophy in the late 20th century. However, there has been very little progress in finding treatment that is specific to this condition. Most of the therapies today target symptoms of the disease, and not the disease itself. Antioxidants, corticosteroids, and physiotherapy are just a few treatments that help patients improve their symptoms.
Researchers have found the mutated gene responsible for FSHD
Each form of muscular dystrophy develops as a result of a mutated gene and other environmental factors. These mutated genes either lead to the formation of a toxic compound, or the failure to produce specific compounds for muscular growth.
Recently, researchers have discovered that the progressive loss of muscles in FSHD is caused by the DUX4 gene. The DUX4 gene creates a protein that is toxic to muscular cells. We usually do not have this protein in our muscular cells, however, those with FSHD have this protein present. This protein causes progressive cell death in FSHD patients, which eventually makes them experience progressive muscular weakness.
A team of researchers from the Department of Biochemistry and Molecular Biology of Saint Louis University decided to look for the exact molecules that could alter the functioning of the DUX4 gene to slow down the disease's progression.
This team's approach was different than most. Instead of looking for something that is totally new, they looked into the effects of various drugs that already exist. However, these drugs have not been used to treat any form of muscular dystrophy. After learning the molecular structure of FSHD as a disease, these researchers wanted to see if there could be a new approach that specifically targets the DUX4 gene.
They screened a massive number of drugs to find which drugs could alter or completely shut down the production of the DUX4 protein. They eventually found two groups of drugs that can have this effect, beta-2 adrenergic (beta agonists) medicinces and medicaments that can inhibit bromodomain and extra-terminal (BET) proteins.
The upside of these findings is that these drugs are already approved and being used to treat other diseases.
Beta-agonists have been used in clinical settings for more than half a century. These drugs usually treat asthma and other conditions related to broncho-constriction, and target specific cardiac issues. The BET inhibitors, however, have been researched for approximately a decade, and are used to treat various forms of cancer.
However, this is only a start. We still need further research to understand how these treatments could help FSHD patients. If these drugs could be an option for patients, then patients could be treated with them very soon. This team's findings can also help identify other remedies that can control how this gene presents itself.
References
- Denny AP, Heather AK. Are Antioxidants a Potential Therapy for FSHD? A Review of the Literature. Oxidative Medicine and Cellular Longevity. 2017;2017. doi:10.1155/2017/7020295.
- Tassin A, Laoudj-Chenivesse D, Vanderplanck C, et al. DUX4 expression in FSHD muscle cells: how could such a rare protein cause a myopathy? J Cell Mol Med. 2013;17(1):76-89. doi:10.1111/j.1582-4934.2012.01647.x.
- Himeda CL, Debarnot C, Homma S, et al. Myogenic Enhancers Regulate Expression of the Facioscapulohumeral Muscular Dystrophy-Associated DUX4 Gene. Mol Cell Biol. 2014;34(11):1942-1955. doi:10.1128/MCB.00149-14.
- Himeda CL, Debarnot C, Homma S, et al. Myogenic Enhancers Regulate Expression of the Facioscapulohumeral Muscular Dystrophy-Associated DUX4 Gene. Mol Cell Biol. 2014;34(11):1942-1955. doi:10.1128/MCB.00149-14.
