Mendell J R, Kissel J T, Amato A A, King W, Signore L, Prior T W, Sahenk Z, Benson S, McAndrew P E, Rice R
Department of Neurology, Ohio State University, Columbus 43210, USA.
N Engl J Med. 1995 Sep 28;333(13):832-8. doi: 10.1056/NEJM199509283331303.
Myoblast transfer has been proposed as a technique to replace dystrophin, the skeletal-muscle protein that is deficient in Duchenne's muscular dystrophy. Donor myoblasts injected into muscles of affected patients can fuse with host muscle fibers, thus contributing their nuclei, which are potentially capable of replacing deficient gene products. Previous controlled trials involving a single transfer of myoblasts have been unsuccessful.
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 arms served as sham-injected controls. In each procedure 110 million cells 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 after the final myoblast transfer, the presence of dystrophin was assessed with the use of peptide antibodies specific to the deleted exons of the dystrophin gene.
There was no significant difference in muscle strength between arms injected with myoblasts and sham-injected arms. In one patient, 10.3 percent of muscle fibers expressed donor-derived dystrophin after myoblast transfer. Three other patients also had a low level of donor dystrophin (< 1 percent); eight had none.
Myoblasts transferred once a month for six months failed to improve 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 muscular dystrophy who had a high percentage of donor-derived dystrophin. Specific variables affecting the efficiency of myoblast transfer need to be identified in order to improve upon this technique.
成肌细胞移植已被提议作为一种替代抗肌萎缩蛋白的技术，抗肌萎缩蛋白是杜兴氏肌营养不良症患者体内缺乏的一种骨骼肌蛋白。将供体成肌细胞注入受影响患者的肌肉中，可与宿主肌纤维融合，从而贡献其细胞核，这些细胞核有可能替代缺失的基因产物。先前涉及单次成肌细胞移植的对照试验均未成功。
我们对12名患有杜兴氏肌营养不良症的男孩，每月向其一只手臂的肱二头肌注射一次供体肌肉细胞，持续六个月。另一只手臂作为假注射对照。在每次操作中，转移由父亲或兄弟捐赠的1.1亿个细胞。患者被随机分配接受环孢素或安慰剂治疗。通过定量等长肌肉测试来测量肌力。在最后一次成肌细胞移植六个月后，使用针对抗肌萎缩蛋白基因缺失外显子的肽抗体评估抗肌萎缩蛋白的存在情况。
注入成肌细胞的手臂与假注射手臂之间的肌肉力量没有显著差异。在一名患者中，成肌细胞移植后10.3%的肌纤维表达了供体来源的抗肌萎缩蛋白。另外三名患者也有低水平的供体抗肌萎缩蛋白（<1%）；八名患者没有。
每月注射一次成肌细胞，持续六个月，未能改善杜兴氏肌营养不良症患者的力量。在一名供体来源抗肌萎缩蛋白比例较高的杜兴氏肌营养不良症患者中，证明了外显子特异性肽抗体在解释成肌细胞移植结果中的价值。为了改进这项技术，需要确定影响成肌细胞移植效率的具体变量。
