MYOBLAST TRANSFER IN THE TREATMENT OF DUCHENNES MUSCULAR-DYSTROPHY
MYOBLAST TRANSFER IN THE TREATMENT OF DUCHENNES MUSCULAR-DYSTROPHY
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DOI：
10.1056/nejm199509283331303
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发表时间：
1995-09-28
影响因子：
158.5
通讯作者：
BURGHES, AHM
中科院分区：
文献类型：
--
作者：
MENDELL, JR;KISSEL, JT;BURGHES, AHM
背景成肌细胞转移已被提出作为一种技术，以取代dystrophin，血管肌肉蛋白是缺乏杜氏肌营养不良症。将供体成肌细胞注射到受影响患者的肌肉中可以与宿主肌纤维融合，从而贡献其细胞核，这可能能够替代缺陷的基因产物。以前的对照试验涉及成肌细胞的单次转移一直不成功。我们每月一次将供体肌肉细胞注射到12名杜氏肌营养不良症男孩的一只手臂的肱二头肌肌肉中，持续6个月。对侧臂作为假注射对照。在每个程序中，由父亲或兄弟捐赠的1.1亿个细胞被转移。患者被随机分配接受环孢霉素或安慰剂。通过定量等长肌肉测试测量力量。在最终的成肌细胞移植后6个月，使用抗肌萎缩蛋白基因缺失外显子的特异性肽抗体评估抗肌萎缩蛋白的存在。注射成肌细胞的手臂和假注射的手臂之间的肌肉力量没有显著差异，在一名患者中，10.3%的肌纤维在成肌细胞移植后表达供体来源的肌营养不良蛋白，另外三名患者也有低水平的供体肌营养不良蛋白（
Background. 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.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 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.Results. 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 (