Dystrophin Gene Repair in mdx Mouse Myoblasts and Bone Marrow Cells as a Basis for Autologous Transplant in Human DMD

肌肉营养不良是一种遗传性疾病，会导致肌肉萎缩和严重残疾。最严重的形式会导致新生儿过早死亡，但大量儿童表现出早期轻微症状，并在青少年和年轻成人中稳步发展为严重残疾形式。这些营养不良中最具破坏性的可能是杜氏肌营养不良症(DMD)。这种情况影响每3300名男孩中就有一名，他们在大约5岁时出现症状，直到十几岁时坐轮椅分娩。DMD男孩接受了主要的临床和手术治疗，目前这些治疗只对他们的生活有很小但重大的改善。杜兴男孩的死亡年龄中值为22岁。DMD的病因已经知道了近20年，只是肌肉中单一成分的缺陷，肌营养不良蛋白是由肌肉细胞产生的。一般来说，患有DMD的男孩都有肌营养不良蛋白，它缺少一个重要的部分，可以防止肌肉在运动时崩溃。因此，DMD男孩的所有肌肉在他们的一生中都会慢慢分解，直到他们死亡，因为帮助呼吸的肌肉(横隔膜)不再能够帮助他们呼吸。肌营养不良蛋白是由一个基因(dys基因)产生的，dystrophin的缺陷是由dys基因缺陷引起的。如果患有DMD的男孩的dys基因缺陷能够得到纠正，他们的dystrophin也可能得到纠正，并防止他们的肌肉崩溃。我们已经能够纠正患有DMD的小鼠肌肉细胞中的dys基因。我们希望改进这项技术，允许肌肉中重新种植经过基因修正的细胞，为治疗人类DMD奠定基础。通过这种方式，我们希望显着改善和延长这些男孩的寿命，甚至可以治愈DMD和其他遗传性肌肉疾病。

The muscular dystrophies are inherited diseases that lead to muscle wastage and severe disabilities. The most severe forms result in the early death of newborns, but a large number are diagnosed in children showing early mild symptoms and progress steadily to severe disabling forms in the juvenile and young adult. Perhaps the most devastating of these dystrophies is Duchenne Muscular Dystrophy (DMD). This condition affects 1 in 3,300 boys, who show symptoms at around 5 years of age until wheelchair confinement by early teens. DMD boys undergo major clinical and surgical treatments which at present only provide small but significant improvements to their lives. The median age at death for Duchenne boys is 22 years. The cause of DMD has been known for almost 2 decades and is a defect in just a single component of muscle, Dystrophin which is produced by muscle cells. In general, boys with DMD possess Dystrophin which is missing an important part that prevents the breakdown of muscles during activity. As a consequence, all the muscles in DMD boys slowly break down over their lifetime until they die because the muscle which helps in drawing breath (Diaphragm) is no longer capable of helping them to breathe. The muscle component Dystrophin is produced by a gene (the dys gene) and the defect of Dystrophin is caused by a defect in the dys gene. If the dys gene defect was able to be corrected in boys with DMD, their Dystrophin may also be corrected and the breakdown of their muscle prevented. We have been able to correct the dys gene in muscle cells from a mouse with DMD. We wish to improve this technology and allow muscle to be repopulated with genetically corrected cells to form a basis for treatment of human DMD. In this way we hope to significantly improve and lengthen these boys' lives and even lead to a cure for DMD and other genetic muscle diseases.