MYOBLAST TRANSFER IN THE TREATMENT OF DUCHENNES MUSCULAR-DYSTROPHY

Background. Myoblast transfer has been proposed as a technique to repl ace dystrophin, the skeletal-muscle protein that is deficient in Duche nne's muscular dystrophy. Donor myoblasts injected into muscles of aff ected patients can fuse with host muscle fibers, thus contributing the ir nuclei, which are potentially capable of replacing deficient gene p roducts. Previous controlled trials involving a single transfer of myo blasts have been unsuccessful. Methods. We injected donor muscle cells once a month for six months to the biceps brachii muscles of one arm of each of 12 boys with Duchenne's muscular dystrophy. The opposite ar ms served as sham-injected controls. In each procedure 110 million cel ls donated by fathers or brothers were transferred. The patients were randomly assigned to receive either cyclosporine or placebo. Strength was measured by quantitative isometric muscle testing. Six months afte r the final myoblast transfer, the presence of dystrophin was assessed with the use of peptide antibodies specific to the deleted exons of t he dystrophin gene. Results. There was no significant difference in mu scle strength between arms injected with myoblasts and sham-injected a rms, In one patient, 10.3 percent of muscle fibers expressed donor-der ived dystrophin after myoblast transfer, Three other patients also had a low level of donor dystrophin (<1 percent); eight had none, Conclus ions. Myoblasts transferred once a month for six months failed to impr ove strength in patients with Duchenne's muscular dystrophy. The value of exon-specific peptide antibodies in the interpretation of myoblast transfer results was demonstrated in a patient with Duchenne's muscul ar dystrophy who had a high percentage of donor-derived dystrophin. Sp ecific variables affecting the efficiency of myoblast transfer need to be identified in order to improve upon this technique.