Facioscapulohumeral muscular dystrophy (FSHMD, FSHD or FSH) is an autosomal dominant inherited form of muscular dystrophy (MD). This type of MD, affects the skeletal muscles of the face (facio), scapula or shoulder blade (scapulo) and upper arms (humeral).
FSHD is the third most common genetic disease of the skeletal muscle affecting 1 in 8,000 people, however no treatment is available for this condition. The lack of experimental models of FSHD has hampered the understanding of the disease, thus inhibiting progress in development of therapies.
In new research published in Stem Cells Translational Medicine, researchers have developed a Facioscapulohumeral muscular dystrophy-affected skeletal muscle model using human pluripotent stem cells. The model provides for a better option in comparison to invasive patient biopsies.
The model involves a scalable monolayer system that differentiates the human embryonic stem cells (hESCs) into mature skeletal muscle cells (SkMCs) within 26 days without any genetic manipulation.
Generally, SkMCs are derived from hESCs by the forced expression of myogenic factors, generation of 3D embryoid bodies or extensive cell sorting, which limit the quantity or consistency of SkMCs produced thus hampering their drug screening usability. In the present report, a novel and renewable method for creating phenotypes of FSHD1-affected myotubes that are suitable for therapeutic screening applications.
First author of the published article and Principle Investigator of the study, Dr. Leslie Caron said, “I would say that to date, there is no accurate animal model for muscular dystrophies. The most commonly used models are patients muscle biopsies which present obvious limitations. Lack of a suitable cellular model for muscle diseases was stunting research into diseases like FSHD, with very little known and no progress in therapeutics. We hope that our work will facilitate research and especially drug development for FSHD and muscular dystrophies in general.”
“Our study demonstrates disease-specific phenotypes in muscle derived from both human embryonic and induced pluripotent stem cells affected with FSHD. These cells represent a scalable resource that provides many advantages over invasive patients biopsies and provides an invaluable tool for drug screening and the development of new therapies against FSHD. This study may also provide new insight into FSHD pathology. As these cells are embryonic in nature, they allow the identification of new pathways associated with the early stages of the disease.”