PENTOXIFYLLINE AS A RESCUE TREATMENT IN DUCHENNE MUSCULAR DYSTROPHY

己酮可可碱作为杜氏肌营养不良症的抢救治疗

• 批准号: 7603407
• 负责人: ALAN PESTRONK
• 金额: $ 0.05万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603407
• 关键词: 2-methylcyclopentadienyl manganese tricarbonyl; Antigens; CD4 Positive T Lymphocytes; CD8-Positive T-Lymphocytes; Computer Retrieval of Information on Scientific Projects Database; Contracture; Defect; Dendritic Cells; Dose; Double-Blind Method; Duchenne muscular dystrophy; Dystrophin; End Point; Evaluation; Failure; Fibrosis; Flexor; Funding; Genes; Genetic Counseling; Grant; Hand; Immune response; Incidence; Institution; Leg; Life; Measurement; Measures; Mediating; Medical Research; Membrane; Muscle; Muscle Weakness; Muscular Dystrophies; Mutation; Natural regeneration; Patients; Pentoxifylline; Placebos; Population; Process; Pulmonary function tests; Quality of life; Randomized; Rate; Research; Research Personnel; Resources; Score; Scoring Method; Screening procedure; Source; Steroids; Testing; Time; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Upper arm; X Chromosome; grasp; human TNF protein; male; mast cell; muscle necrosis; muscle strength; neutrophil; wasting

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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 DMD是最常见和最具破坏性的肌营养不良症，全球发病率为每3500名男性中就有一名，其特征是肌营养不良蛋白完全丧失，导致进行性肌肉无力和消瘦。DMD的主要缺陷是X染色体短臂上的dystrophin基因突变。由于该基因非常大，有很高的自发突变率，不可能通过遗传咨询和筛查来根除DMD。肌营养不良蛋白缺乏引发的病理生理级联导致肌膜不稳定和渗漏，导致肌肉坏死、纤维化和再生失败。参与这一过程的一个机制是由肥大细胞、抗原提呈树突状细胞、CD4和CD8淋巴细胞以及多形核细胞介导的免疫反应。 这是一项为期12个月的多机构、双盲、随机研究。64名DMD患者将随机接受PTX或安慰剂治疗。评估包括QMT、MMT、定时功能测试、肺功能测试、肌挛缩测量和生活质量。要研究的人群是：男性，7-100岁，流动，12个月剂量稳定的类固醇。主要终点是比较接受PTX治疗和服用安慰剂的受试者的肌肉力量(使用CQMS测量)。记录了连续两次最大努力的最高值。次要终点包括手臂、腿部和握力QMT评分(由成对的屈肌和伸肌以及手握力组成)、MMT评分(使用改进的医学研究委员会的肌肉力量评分方法测量)、功能评估、时间功能测试、PFT、PQOL、测角、肿瘤坏死因子α和转化生长因子β。