The role of macrophages in Facioscapulohumeral muscular dystrophy

Investigator: Andreia M Nunes PhD

Category: Research - Basic

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive disease that affects the muscles. The affected muscles show an increase in the number of immune cells. Immune cells are responsible for defending the body, but the role of these cells in FSHD is not understood. Macrophages, a type of immune cell, interfere with the progression of other muscle diseases such as Duchenne muscular dystrophy. These cells have a memory of previous challenges and are overreactive in Duchenne muscular dystrophy. However, it is unknown if macrophages are also overreactive in FSHD. Besides that, bacterial infections cause a type of muscle disease called infectious myositis. This indicates that infections might impair muscle function in some diseases. Nevertheless, it is still unknown if bacterial infections affect the progression and severity of FSHD. Mice are a tool for studying FSHD, but mice only have 10% of their immune system similar to humans. In contrast, the pig is more than 80% similar to humans. The Jones' team recently created a new pig model that recapitulates human FSHD.

In this study, I propose to use this pig model to study the immune response in FHSD. I propose to determine if macrophages are overreactive in FSHD and if bacterial infections increase the severity of FSHD. In aim 1, I will evaluate pigs throughout their life to test if multiple activations of DUX4 induce alterations in macrophages. In aim 2, I will mimic a bacterial infection in pigs and test if the macrophages are altered. I will validate the discoveries of this project in human samples. This study will reveal how the immune response affects FSHD. This new knowledge will help identify new biomarkers for clinical trials.

Upon approval this grant will continue for a second year at an additional $99,669.

Related Material

Report 1