Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne muscular dystrophy boys.
Five billion normal myoblasts were injected into each of 21 Duchenne muscular dystrophy (DMD) boys aged 6-14 yr to assess the feasibility, safety, and efficacy of the Phase II myoblast transfer therapy (MTT). The Phase II study was designed to strengthen muscles of both lower limbs. Forty-eight intramuscular injections transferred the myoblasts into 22 major muscles at 55.6 x 10(6)/mL in 10 min under general anesthesia. Eleven boys had received 8 million myoblasts each 1 yr ago in the Phase I MTT. In the Phase II study, eight of them had their myoblasts subcultured from reserves frozen 1 yr ago. The donor myoblasts for each of the remaining boys were cultured from satellite cells derived from a 1-g muscle biopsy of a normal male who might or might not be histocompatible with the recipient. The immunosuppressant cyclosporine (Cy) is being administered to recipients for 6 mo after MTT to facilitate donor cell survival. There was no evidence of an adverse reaction to MTT or Cy as determined by serial laboratory evaluations including electrolytes, creatinine, and urea. Early objective functional tests using the KinCom Robotic Dynamometer were conducted on 13 subjects aged 6 to 13 before MTT and at 3 mo after MTT. Of the 69 muscle groups (knee extensors, knee flexors, plantar flexors) tested for isometric force generation in these subjects, 43% showed mean increase of 41.3% +/- 5.9 SEM, 38% showed no change, and 19% showed continuous force reduction of 23.4% +/- 3.1 SEM. The remaining subjects await the 3-mo post-MTT evaluation. The results indicate that 1) MTT is safe; 2) MTT increases muscle strength in DMD: 81% of the muscles tested showed either increase in strength or did not show continuous loss of strength; 3) more than 5 billion myoblasts can be cultured from 1 g normal muscle biopsy, providing unprecedented numbers of cells for MTT; 4) myoblasts, frozen over 1 yr, retain the ability to proliferate from 10 million to 5 billion, and to form normal myofibers; 5) injections of 5 billion myoblasts have not provoked any immunological rejection symptoms in the Phase II subjects, 11 of whom received 8 million myoblasts in the Phase I MTT a year ago; 6) it is safe to perform multiple injections of myoblasts into lower limb muscles without formation of emboli; and 7) donor cell rejection by the recipient can be prevented with Cy when properly managed.