Understanding the molecular processes that cause the progression of FSHD  

FSHD is caused by genetic changes that lead to a gene called DUX4 being switched on when it shouldn’t be. DUX4 itself causes other genes to be switched on. It’s thought that it’s this action that makes DUX4 harmful to muscles, leading to their premature wasting. Genes generally work in partnership with other genes, with instructions being passed down the pathway to ensure everything within cells and tissues works correctly. However, it’s still not understood how DUX4 contributes to muscle wasting in people with FSHD and how it affects the instructions being passed along the pathway. It’s also unclear which specific cells are involved in this unknown process, and at what stage of the condition. 

Using new technologies, researchers can now study different genes within cells and see if and how these genes communicate with each other within a pathway. It provides a type of map called spatial representation which shows where specific genes are active or inactive in a muscle obtained through muscle biopsy. This approach can make a difference in understanding how DUX4 causes damage to muscle cells, and how the damage leads to inflammation of these muscle cells before they are replaced with fat.  

The researchers aim to identify important biological processes, such as inflammation and fibrosis (the replacement of muscle by fat and scar tissue) and understand where in cells these processes start in muscle samples of people with FSHD. They will also look to understand if specific cells are involved in these processes. The team has already collected the biopsy samples as part of another study. 

This research project could improve understanding of the underlying causes and processes of FSHD and could help the future development and testing of treatments for this condition.