Myoblast Transfer Therapy for Duchenne Muscular Dystrophy

Abstract

A randomly selected extensor digitorum brevis (EDB) muscle in each of three Duchenne muscular dystrophy (DMD) boys aged 9 to 10 was injected with approximately 8 x 106 myoblasts. The contralateral EDBs were sham-injected with carrier solution. Donor myoblasts were derived from cell culture of muscle biopsies from the normal ward or normal brothers of the recipients. Cyclosporine (CsA) treatment began two days before myoblast injection and continued for three months. Three days prior to myoblast injection and three months after, the isometric twitch and maximum voluntary contraction of the left and the right EDBs were measured. Myoblast-injected EDBs showed increases in tensions whereas sham-injected EDBs showed reductions. Both immunocytochemical staining and immunoblot revealed dystrophin in the myoblast-injected EDBs. Dystrophic characteristics such as fiber splitting, central nucleation, phagocytic necrosis, variation in fiber shape and size, and infiltration of fat and connective tissues were less frequently observed in these muscles. Sham-injected EDBs exhibited significant structural and functional degeneration and no dystrophin. Throughout the study, there was no sign of erythema, swelling or tenderness at the injection sites. Serial laboratory evaluation including electrolytes, creatinine, and urea did not reveal any significant changes before or after myoblast transfer. We conclude that myoblast transfer therapy is a safe and efficacious procedure to improve the biochemistry, structure, and function of degenerative EDB muscles in DMD.

Repairing skeletal muscle: regenerative potential of skeletal muscle stem cells

“…In 1990, Peter Law and collaborators reported the first SC transplant in a 9-year-old boy affected by DMD, showing safety and dystrophin production (93). Soon after, 11 clinical trials in DMD patients were conducted using intramuscular injection of SCs (Table 3) (94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104). Although there were no adverse effects, new dystrophin production was demonstrated in many but not all cases and clinical benefit in none (6,105).…”

Myoblast transfer and gene therapy in muscular dystrophies

“…However, the design of these and of further experiments (Law et al, 1991Thompson, 1992a;"remblay et al, 1993) has made it very difficult to determine whether mpc implantation can be considered a possible therapy for DMD. These results did, nonetheless, highlight many features which could be more easily studied in animal models rather than in humans.…”

Biological characteristics of muscle-derived satellite cells isolated from rats at different postnatal days

“…In 1991, Law et al (1991) transplanted MDSCs for the treatment of Duchenne muscular dystrophy for the first time. Although the overall effect was poor, MDSCs still demonstrated good potential for the treatment of this myopathy.…”