Cell transplantation as an experimental treatment for Duchenne muscular dystrophy.

The feasibility, safety, and efficacy of myoblast transfer therapy (MIT) were assessed in an experimental lower body treatment (LBT) involving 32 Duchenne muscular dystrophy (DMD) boys aged 6-14 yr, half of whom were nonambulatory. Through 48 injections, five billion (55.6 x 10(6)/mL) normal myoblasts were transferred into 22 major muscles in both lower limbs, in 10 min with the subject under general anesthesia. Ten subjects received myoblasts cultured from satellite cells derived from 1-g fresh muscle biopsies of normal males aged 9-21 yr. Donor myoblasts for the remaining 22 boys were subcultured from reserves frozen 1 mo-1.5 yr ago. Only four donors were known to have identical histocompatibility with their recipients. All subjects took oral doses of the immunosuppressant cyclosporine (Cy), beginning at 2 days before MTT and lasting 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. Objective functional tests using the KinCom Robotic Dynamometer measured the maximum isometric contractile forces of the ankle plantar flexors (AF), knee flexors (KF), and knee extensors (KE) before MTT and at 3, 6, and 9 mo after MTT. The AF, being distal muscles and less degenerative than the KE and the KF, showed no decrease in mean contractile force 3 mo after MTT, and progressive increases in force at 6 and 9 mo after MTT. At 9 mo after MTT, 60% of the 60 AF examined showed a mean increase of 50% in force; 28% showed no change; and only 12% showed a mean decrease in force of 29% when compared to the function of the same muscles before MTT. The KF, being proximal muscles and more degenerative, showed no change in function at 9 mo after MTT. The KE, being proximal and anti-gravitational, were most degenerative before MTT. They showed no statistically significant change in force at 3 mo after MTT but showed decreases at 6 and 9 mo after MTT. At 9 mo after MTT, 23% of the 60 KE examined showed a mean increase of 65% in force; 22% showed no change; and 55% showed a mean decrease of 24% in force. When results of all muscle groups (AF, KF, KE) were pooled, there was no change in force at 3, 6, or 9 mo after MTT vs. before MTT according to the Wilcoxon signed rank test.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

Effect of electrical stimulation on quadriceps strength after reconstructive surgery of the anterior cruciate ligament.

The effect of prolonged daily electrical stimulation (ES) on quadriceps strength in 22 patients during the 6 weeks following anterior cruciate reconstruction was investigated. Patients were randomly assigned to receive either a combination of ES and exercise or exercise alone. Isometric quadriceps strength was measured at the 7th, 8th, and 9th postoperative weeks. No significant difference in strength existed between the groups as a result of ES. A significant difference in strength did exist between competitive and recreational athletes regardless of treatment. Further research is needed to determine if the addition of ES to isometric exercise during immobilization can significantly retard strength loss after anterior cruciate reconstructive surgery.