Grant: Operating Grant

The transplantation of muscle precursor cells (MPCs) is a potential treatment for several recessive muscular dystrophies (although the research has been focused mainly on Duchenne Muscular Dystrophy). To restore the expression of a gene, which is defective in the patient muscle fibers the transplanted MPCs have to fuse with these muscle fibers. The proliferation and fusion of MPCs is limited by a negative growth factor (called myostatin), which is produced by the muscle fibers themselves. Myostatin limits the duration of the muscle fiber regeneration after MPC transplantation and also prevent muscle fibers from becoming bigger and stronger. Myostatin thus reduces the success of MPC transplantation. The aim of this grant proposal is to improve the success of MPCs transplantation by modifying the transplanted MPCs so that they cannot be inhibited by myostatin. Since the patient own MPCs would still be sensitive to the myostatin inhibition this would give a proliferating and a fusion advantage to the transplanted cells and thus improves the success of MPC transplantation evaluated by the number of muscle fibers expressing the normal gene (i.e., dystrophin in the case of DMD). Blocking the myostatin signal will also permit to obtain bigger and stronger muscle fibers and will thus hopefully permit to increase the strength of the muscles transplanted with MPCs.