Results of a triple blind clinical study of myoblast transplantations without immunosuppressive treatment in young boys with Duchenne muscular dystrophy.

The effects of myoblast transplantations without an immunosuppressive treatment on muscle strength, and the formation of dystrophin-positive fibers was studied in five young boys with Duchenne muscular dystrophy (DMD) using a triple blind design. Injections of myoblasts were made into one biceps brachii (BB), and the opposite BB, used as a control, was sham-injected; the experimenters and the patient were blind to the myoblast-injected side. At the same time, myoblasts were also injected in the left tibialis anterior (TA) of these patients. The strength developed during maximal static contractions of the elbow flexor and extensor muscles was measured with a Kin-Com dynamometer. No increase in static elbow flexion torque was measured at any time from 2 mo up to 18 mo after the transplantation. One month after the transplantation, the percentage of dystrophin-positive fibers in the myoblast-injected TA ranged from 0 to 36%, while it ranged from 0 to 4% on the control side. The expression of dystrophin in these fibers, however, was generally low, and most likely less than 10% of the normal level. In the biceps brachii of both sides 6 mo after the transplantation, less than 1.5% of dystrophin-positive fibers were detected. The injections also triggered a humoral immune response of the host. Antibodies were capable of fixing the complement, and of lysing the newly formed myotubes. One of the antigens recognized by this immune response is possibly dystrophin. These results strongly suggest that myoblast transplantations, as well as gene therapy for DMD, cannot be done without immunosuppression.