31. Dystrophin Expression in Muscles of Duchenne Muscular Dystrophy Patients Following High-Density Injections of Normal Myogenic Cells

A clinical trial was conducted to test a new protocol of normal muscle-precursor cell (MPC) allotransplantation in skeletal muscles of Duchenne muscular dystrophy (DMD) patients. The protocol consisted on using high-density cell-injections as a method for cell delivery and a tacrolimus-based immunosuppression as a method to control acute rejection. Cultured MPCs obtained from one of the patient's parents were implanted in 0.25 or 1 cm3 of a Tibialis anterior in 9 DMD patients. MPC injections were placed 1 to 2 mm from each other, and a similar pattern of saline injections was done in the contralateral muscle. The patients were immuno-suppressed with tacrolimus. Muscle biopsies were performed at the injected sites 4 weeks later. In the biopsies of the cell-grafted sites, there were myofibers expressing donor's dystrophin in 8 patients. The percentage of myofibers expressing donor's dystrophin varied from 3.5% to 26%. Evidence of small-myofiber neoformation was observed in some patients. Donor-derived dystrophin transcripts were detected by RT-PCR in the cell-grafted sites in all patients. The protocol of immunosuppression was sufficient to obtain these results, although it is not certain whether acute rejection was efficiently controlled in all the cases. In conclusion, intramuscular allotransplantation of normal MPCs can induce the expression of donor-derived dystrophin in skeletal muscles of DMD patients, although this expression is restricted to the sites of MPC injection.