14/01/04: Molecular Therapy, 2004 : Dystrophin Expression in Myofibers of Duchenne Muscular Dystrophy Patients Following Intramuscular Injections of Normal Myogenic Cells 

Daniel Skuk, Brigitte Roy, Marlyne Goulet, Pierre Chapdelaine, Jean-Pierre Bouchard, Raynald Roy, Francine J. Dugre, Jean-Guy Lachance, Louise Deschenes, Helene Senay, Michel Sylvain, and Jacques P. Tremblay1,

E-mail: Jacques-P.Tremblay@crchul.ulaval.ca.

Three Duchenne muscular dystrophy (DMD) patients received injections of myogenic cells obtained from skeletal muscle biopsies of normal donors. The cells (30 106) were injected in 1cm3 of the tibialis anterior by 25 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 amounting to 9 (patient 1), 6.8 (patient 2), and 11% (patient 3). Since patients 1 and 2 had identified dystrophin-gene deletions these results were obtained using monoclonal antibodies specific to epitopes coded by the deleted exons. Donor dystrophin was absent in the control sites. Patient 3 had exon duplication and thus specific donor-dystrophin detection was not possible. However, there were fourfold more dystrophin-positive myofibers in the cell-grafted than in the control site. Donor-dystrophin transcripts were detected by RT-PCR (using primers reacting with a sequence in the deleted exons) only in the cell-grafted sites in patients 1 and 2. Dystrophin transcripts were more abundant in the cell-grafted than in the control site in patient 3. Therefore, significant dystrophin expression can be obtained in the skeletal muscles of DMD patients following specific conditions of cell delivery and immunosuppression.