Investigator: Prof. Dr. Arend Heerschap
Category: Research - Clinical
The discovery of the DUX4 gene as the genetic cause for FSHD is a great breakthrough and the development of new treatments focuses on this genetic abnormality. However, to develop and evaluate successful treatments it is equally important to understand what mechanism initiates the production of toxic DUX4 proteins and also to develop objective and quantitative biomarkers for therapy evaluation.
The loss of muscle strength in FSHD is strongly related to the replacement of muscle tissue by fat, and by muscle cell loss and reduction of muscle cell size. Magnetic Resonance Imaging (MRI) is an ideal tool to investigate these muscular pathological changes, because it allows quantitative assessment of the intramuscular fat percentage and muscle volume. Also, patients can be subjected to multiple exams without any risk or harm. We have discovered that within affected thigh muscles the fat content is highest near the knee (distally) and less near the hip (proximally), i.e. there is proximo-distal gradient in fat infiltration. This indicates that the disease starts near the distal tendons.
In this study we want to obtain MR images of whole leg muscles to more precisely establish fatty infiltration patterns, which will identify where the disease starts and may give clues what mechanisms are responsible for disease initiation. Moreover, the shape of the fatty infiltration pattern will help us to characterize how the disease progresses in individual muscles and enable a better diagnosis of the severity of the disease. Furthermore, we will evaluate leg muscles of a number of FSHD patients by MRI over about 3 years, which will give us an idea if we can predict fatty infiltration and disease progression for an individual muscle.
This study requires the analysis of a large amount of muscles, which is hampered by the standard way of manual segmentation of muscles. To enhance the speed of analysis we will use a newly developed (semi-)automatic muscle segmentation tool in this project, which may also be valuable in the evaluation by MRI of clinical trials in FSHD.
To summarize, this study aims to perform a longitudinal whole muscle MRI assessment of the lower extremity muscles in FSHD patients to capture disease initiation and the direction of progression with analysis by semi-automatic segmentation software.