PENTOXIFYLLINE AS A RESCUE TREATMENT IN DUCHENNE MUSCULAR DYSTROPHY

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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.