PENTOXIFYLLINE AS A RESCUE TREATMENT IN DUCHENNE MUSCULAR DYSTROPHY

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 DMD是最常见和最具破坏性的肌营养不良症类型，全世界发病率为1/3500活产男性，其特征在于肌营养不良蛋白的完全丧失，导致进行性肌无力和消瘦。 DMD的主要缺陷是X染色体短臂上的肌营养不良蛋白基因突变。由于这个基因非常大，有很高的自发突变率，通过遗传咨询和筛查来根除DMD是不可能的。 由肌营养不良蛋白缺乏触发的病理生理级联反应导致不稳定和渗漏的肌肉膜，导致肌肉坏死、纤维化和再生失败。 该过程中涉及的一种机制是由肥大细胞、抗原呈递树突细胞、CD 4和CD 8淋巴细胞以及多形核细胞介导的免疫应答。 这是一项为期12个月、多机构、双盲、随机化研究。 64名DMD患者将被随机分配接受PTX或安慰剂治疗。 评估包括QMT、MMT、定时功能测试、肺功能测试、挛缩测量和生活质量。 研究人群为：男性，7-100岁，非卧床，类固醇稳定剂量12个月。 主要终点是PTX治疗受试者和安慰剂治疗受试者之间的肌肉强度比较（使用CQMS测量）。 记录两个连续的最大努力的最高值。 次要终点包括手臂、腿部和抓握QMT评分（包括成对的屈肌和伸肌以及手部抓握）、MMT评分（使用改良的医学研究理事会肌肉力量评分方法测量）、功能评价、时间功能试验、PFT、PQOL、测角术、TNF α和TGF β。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DMD, the most common and devastating type of muscular dystrophy with a worldwide incidence of 1 in 3500 live born males, is characterized by complete loss of dystrophin, leading to progressive muscle weakness and wasting. The primary defect in DMD is a mutation in the dystrophin gene on the short arm of the X chromosome. Because this gene is very large, there is a high spontaneous mutation rate and eradication of DMD by genetic counseling and screening impossible. The pathophysiological cascade triggered by lack of dystrophin results in unstable and leaky muscle membrane leading to muscle necrosis, fibrosis and failure of regeneration. One mechanism involved in this process is an immune response mediated by mast cells, antigen-presenting dendritic cells, CD4 and CD8 lymphocytes and polymorphonuclear cells. This is a 12-month, multi-institutional, double-blinded, randomized study. Sixty-four DMD patients will be randomized to either PTX or placebo. Evaluations include QMT, MMT, timed function testing, pulmonary function testing, contracture measurement and quality of life. The population to be studied is: Male, 7-100 years, Ambulant, stable 12-month dose of steroids. The primary endpoint is the comparison of muscle strength (measured using the CQMS) between PTX-treated and placebo-treated subjects. The highest value of two consecutive maximal efforts is recorded. Secondary endpoints include arm, leg and grip QMT scores consisting of paired flexors and extensors as well as hand grip, MMT score (measured using a modified Medical Research Council's muscle strength scoring method), functional evaluations, time function tests, PFT's, PQOL, goniometry, TNF alpha and TGF beta.