Mutation Identification and Therapies
The goal of our project is to better understand the functions of dysferlin, to analyze the fate of abnormal dysferlin protein, and finally to set up a therapeutic trial in human patients affected with dysferlinopathies. The project can be split into three parts and will be performed on a collaborative basis with others labs in the field:
- Identification of dysferlin mutations using various techniques
- Establish cell cultures from control individuals and patients in order to analyze dysferlin's role in plasma membrane supply phenomena, in both physiological (after phagocytosis : monocytes/macrophages) or experimental conditions (mechanical stress and membrane damage : monocytes/macrophages, myoblasts/myotubes).
- According to each mutation's type and position, specific and targeted therapeutic approaches will be addressed first in culture, then in mouse models, before including the patients in therapeutic trials. In collaboration with Généthon and the Institute of Myology, the exon skipping method will be used for homozygous mutations. We also plan to test Aminoglycosides (PTC124) for mutations resulting in a premature STOP codon.