Understanding the causes and consequences of inflammation in FSHD muscular dystrophy to develop a possible treatment

FSHD is a muscle disease caused by aberrant overproduction of the protein DUX4. The mechanism through which DUX4 causes the disease is incompletely known. Recently, the inflammatory molecule IL-6 was identified as the first marker significantly associated with FSHD disease duration, severity, and muscle weakness. While the current data suggest that excessive IL-6 levels could contribute to FSHD, the relevance of IL-6 for the disease has not been directly tested and the source of its production is unknown. Recent data also suggest that alteration in fibro-adipogenic progenitor (FAP) cells could contribute to the disease, but the mechanism responsible for FAP alteration in FSHD is unknown. Our preliminary data provide a possible molecular explanation for the above changes. In this project, we propose a comprehensive analysis combining various approaches to identify the sources of IL-6 production and evaluate the therapeutic relevance in FSHD.