DAILY VS WEEKLY PREDNISONE THERAPY IN DUCHENNE MUSCULAR DYSTROPHY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。杜氏肌营养不良症(DMD)是世界上最常见的遗传性疾病之一。然而，到目前为止，唯一被证明可以改善DMD患者健康和活动能力的临床治疗方法是皮质类固醇激素泼尼松和呋喃西林。两种制剂均具有免疫调节作用，均可减少DMD肌肉中T细胞的侵袭。然而，越来越多的证据表明，更多的病理生理途径在一定程度上与皮质类固醇的疗效有关。包括改善钙稳态，抑制肌肉蛋白质降解，改善能量代谢。虽然许多医生认为长期使用类固醇是DMD的“治疗标准”，但在美国，只有大约一半的医生和患者家庭选择使用类固醇，因为它与长期使用有关的副作用。许多使用类固醇的人将治疗推迟到疾病晚期，因为担心风险大于治疗的好处。用于其他自身免疫性疾病的一些替代方案已被发现对DMD无效；然而，间歇给予大剂量类固醇被发现对其他自身免疫性疾病有效且副作用较少，尚未在充分动力的对照试验中对DMD进行评估。本研究将评估间歇性给药的大剂量泼尼松在儿童DMD患者中的应用。找到一种替代剂量方案，至少与日常治疗一样有效，但有发烧副作用，是这项建议的目标。如果成功，这种方案很可能成为DMD的标准治疗方案，并允许更早开始治疗，这可能更有益。

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. Duchenne muscular dystrophy (DMD) is among the most common of genetic disorders worldwide. Yet, to date, the only clinical treatments that have been shown to improve the health and mobility of DMD patients are the corticosteroids prednisone and deflazacort. Both agents shoe immune modulatory function, and both decreased the invasion of T-cells in DMD muscle. However there is growing evidence that additional pathophysiological pathways are responsible, in part, for the efficacy of corticosteroids. Including improvement of calcium homeostasis, inhibition of muscle protein degradation, and improvement of energy metabolism. While many physicians consider chronic steroid administration as "standard of care" in DMD, only about half of physicians and patient families in the USA opt to use steroids due to the side effects associated with its chronic use. Many of those that use steroid, delay therapy until the disease is advanced because of concern that risks outweigh the benefits of therapy. Some alternate regimes use for other autoimmune diseases have been found to be ineffective in DMD; however, large dose steroid given intermittently, which have been found to be effective and have fewer side effects in other autoimmune disorders, have not been evaluated in DMD in adequately powered controlled trials. This study will evaluate the high dose prednisone adminsitered on an intermittent schedule in pediatric patients with DMD. Finding an alternate dose regimen that would be at least as effective as daily therapy, but has fever side effects is the goal of this proposal. If successful, this regimen would likely become a standard of care in DMD and permit onset of therapy earlier, which might be even more beneficial.