- Prof. Jacques-P. Tremblay, Principal Investigator
- Dr. David Rothstein, Co-Investigator
- CHUL Research Center, Sainte-Foy, Canada
- Development of Central Immunological Tolerance towards Myoblasts Transplantation
Our long-term aim is to develop a treatment to prevent the progressive muscle weakness in Duchenne muscular dystrophy (DMD) patients. Our research group has already demonstrated that the transplantation of muscle precursor cells, called myoblasts, can restore the expression of the protein, called dystrophin, whose absence is responsible for DMD. Following the transplantation of normal myoblasts, dystrophin was expressed in 90% of the muscle fibers of dystrophic mice, who received a drug (tacrolimus) to prevent the rejection of these cells. Similar results have also been obtained in monkeys. We have also recently obtained encouraging results in a new phase I clinical trial of myoblast transplantation in DMD patients also treated with tacrolimus to prevent rejection. However, tacrolimus may increase the risk of cancer.
My collaborator, Dr. Rothstein, has already shown that an antibody (anti-CD45RB) against a protein present on the surface of some cells from the immune system prevents the rejection of skin transplants. We have also recently obtained preliminary results indicating that this antibody also prevents the rejection of myoblasts in mice.
The first aim of this project is, therefore, to improve these preliminary results by performing myoblast transplantation after bone marrow transplantation. The protocol will use two different antibodies against proteins on the cells of the immune system (anti-CD45RB and anti-CD154).
The second aim is to determine the mechanism involved in preventing the rejection of the transplanted cells so that we can improve the treatment.
We hope that this research project will permit the development of a treatment for Duchenne muscular dystrophy, based on the transplantation of the cells involved in the formation of the muscle fibres, into the muscles of the patients. The present research project will enable us to prevent the rejection of these cells without using an anti-rejection drug.