1079. Successful Myoblast Transplantation to Duchenne Muscular Dystrophy Patients

Abstract

Nine Duchenne muscular dystrophy (DMD) patients received injections of myoblasts obtained from skeletal muscle biopsies of normal donors. Cells were injected in 1 cm3 of the Tibialis anterior by 25 or 100 parallel injections. We performed similar patterns of saline injections in the contralateral muscles as controls. The patients received tacrolimus for immunosuppression. Muscle biopsies were performed at the injected sites 4 weeks later. We observed dystrophin-positive myofibers in the cell-grafted sites: in 8 of of 9 patients. In these 8 patients, the percentages of dystrophin positive fibers ranged from 3.5 to 26%. Eight patients had identified dystrophin-gene deletions and thus for four of these patients these results were obtained using mAbs specifically to epitopes coded by the deleted exons. Donor-dystrophin was absent in the control sites. For the other patients there were several folds more dystrophin-positive myofibers in the cell-grafted muscle than in the control muscle. Donor-dystrophin transcripts were detected by RT-PCR (using one primer reacting with a sequence in the deleted exons) in 8 patients. No antibodies were detected in the host serum against the donor myoblasts. Therefore, significant dystrophin expression can be obtained in the skeletal muscles of DMD patients following specific conditions of cell delivery and immunosuppression.