Résumé :
|
Communication n°2 Introduction : Following a similar protocol as we used in monkeys, we observed that myoblast transplantation (MT), tested in only 1cm3 of muscle, systematically restored the expression of normal dystrophin in myofibers of DMD patients. However, MT must be done intramuscularly by a protocol of high-density injections. This protocol was never tested throughout entire skeletal muscles in DMD patients, a requisite to investigate potential functional improvements. Objective : To test the safety and the effects of a high-density injection protocol for intramuscular MT in a DMD patient. Methods : A DMD patient 26 years old, severely affected by the disease, received myoblasts cultured from a normal donor. Cells were delivered by injections as close as 1-mm apart throughout some skeletal muscles in the left arm (biceps brachium, brachoradialis and the thenar and hypothenar groups) and in 2 cm3 of gastrocnemius. Tacrolimus was used for immunosuppression. Histological studies were done in a biopsy performed at the injected site in the gastrocnemius one month after MT. Functional evaluations were done in the left arm up to six months after MT. Results : The only consequences of the procedure were local reactions (acute inflammation, subcutaneous hematoma) that generally resolved in a week. We observed 50% dystrophin-positive myofibers in the cell-grafted site of gastrocnemius, and none in the contralateral, saline-injected site. Some functional improvements were observed in the force and amplitude of flexion in the first metacarpian and the amplitude of flexion-extension in the elbow. Conclusions : A protocol of high-density injections for MT throughout several muscles was done in reasonable surgical delays, and was well tolerated by the patient without severe reactions or sequel. This protocol allows observing many dystrophin-positive myofibers in muscles with severe atrophy and fat infiltration. Functional improvements were observed, in spite of the absence of placebo as control.
|