New insights into biomarkers for the muscle disease FSHD under investigation at LUMC
Researchers at LUMC have used advanced RNA analysis to identify unique biomarkers for the hereditary muscle disease FSHD. Using long-read RNA sequencing techniques, they were able to identify new variants of messenger RNA that are specifically expressed in the muscles of FSHD patients, but not in healthy muscle cells. These biomarkers provide new insights into the role of the DUX4 protein in the disease process and may contribute to improved diagnostics, monitoring of disease progression and the development of more effective therapies.
What is FSHD?
Facioscapulohumeral muscular dystrophy (FSHD) is a rare, hereditary muscle disease that affects around 500,000 people worldwide. The condition is characterised by progressive muscle weakness, often starting in the facial muscles and later spreading to the shoulders and upper arms. The course of the disease varies greatly: some patients experience only mild symptoms, while others eventually become wheelchair-bound. In the Netherlands, there are an estimated 2,000 patients.
The role of DUX4 in FSHD
FSHD is caused by a genetic mutation that leads to abnormal activity of the DUX4 protein in muscle cells. Normally, DUX4 is only active during early embryonic development, where it temporarily activates genes that are important for growth and development. However, in FSHD patients, DUX4 remains undesirably active in muscle tissue, causing damage to the muscles and resulting in inflammation and muscle weakness.
From discovery to application
-
In their research into FSHD biomarkers, scientists at the LUMC used an advanced technique: long-read RNA sequencing. Unlike traditional methods, which only analyse short pieces of RNA, this technique makes it possible to map entire RNA molecules. This allowed the researchers to accurately determine which RNA variants are produced in the muscle tissue of FSHD patients, giving them a better understanding of the role of DUX4 in this disease.
-
Thanks to the application of long-read RNA sequencing, researchers at the LUMC have identified unique RNA variants (isoforms) that are specifically present in the muscle tissue of FSHD patients. These biomarkers offer a valuable tool for mapping the course of the disease and evaluating treatments. The insights provided by these biomarkers can help doctors to better understand the severity and progression of the disease and to develop more targeted future therapies.
-
The discovery of these biomarkers opens up new possibilities for the diagnosis and treatment of FSHD. In the future, doctors will be able to use these biomarkers to better determine how the disease develops and whether therapies are effective. Further research will reveal whether these biomarkers can also be used for less invasive diagnostics via blood tests, thereby reducing the burden on patients and enabling more targeted treatments.
