There is no cure or treatment for facioscapulohumeral muscular dystrophy (FSHD), an illness that starts with facial, shoulder and upper arm weakness and eventually affects nearly all skeletal muscles of those with the disease. But, Saint Louis University researchers are in pursuit of a way to shut down the toxic protein that leads to the illness.
In findings published in the Journal of Pharmacology and Experimental Therapeutics, lead author Fran Sverdrup, Ph.D., associate professor of biochemistry and molecular biology at Saint Louis University, reports that his team has successfully halted the expression of the culprit protein in cell and animal models.
Sverdrup, who was motivated to search for a cure for FSHD after his own daughter was diagnosed with the illness, is encouraged by the findings, which suggest a way forward in developing the first treatment or cure for FSHD.
We have been working to find a safe drug that would 'turn off' the toxic gene that causes FSHD. Now we have demonstrated that we can do this in an animal model with a drug that can be taken in pill form."
Fran Sverdrup, Ph.D., associate professor of biochemistry and molecular biology at Saint Louis University
In normal skeletal muscle, the DUX4 gene is silenced. In patients with FSHD, however, the misexpression of this gene leads to cell death and muscle degeneration. Scientist have been searching for a way to prevent DUX4's expression as a way to halt or reverse the course of the disease. Sverdrup's team found that repurposing an existing drug, a clinically advanced p38 inhibitor, suppressed toxic DUX4 expression in cell and animal models.
Offering further cause for optimism, a biopharmaceutical company has begun a clinical trial of the p38 inhibitor losmapimod in patients, further testing this approach and potentially bringing a cure closer to those who need it.
Other researchers on the study include Jonathan Oliva, Scott Galasinski, Amelia Richey, Amy E. Campbell, Marvin J. Meyers, Neal Modi, Jun Wen Zhong, Rabi Tawil and Stephen J. Tapscott.
Sverdrup's research was supported, in part, by a Saint Louis University Research Institute grant. The award funded a new state-of-the-art near-infrared laserpoint scanner that provides high sensitivity and reliable signals for laboratory work.