Development of a Strength Training Protocol in Duchenne Muscular Dystrophy

描述(申请人提供)：Duchenne肌营养不良症(DMD)是一种衰弱的神经肌肉疾病，会导致肌肉崩溃、虚弱和最终死亡。在过去的40年里，父母们几乎没有得到关于锻炼作为一种维持肌肉功能的治疗策略的潜力的指导。众所周知，大强度运动和离心性收缩会导致营养不良肌肉的肌肉损伤，而肌肉负荷不足会反过来导致肌肉萎缩。最近对啮齿动物模型和较温和形式的肌营养不良症的研究支持了早期的研究，即阻力运动可能对营养不良肌肉的肌肉质量维持有好处。然而，需要对阻力练习的安全性和可行性进行仔细和系统的调查，以考虑将其应用于DMD男孩。这项先导性研究的总体目标是评估是否可以安全地在患有DMD的男孩中实施中等强度的强化运动计划。在目标1中，我们将确定轻度到中等强度等长阻力运动在DMD儿童中的剂量反应和安全性。12名患有DMD的流动男孩将参加等长运动剂量方案，在该方案中，负荷逐渐增加。在这项早期概念验证的初步研究中，将研究两大肌肉群：膝关节伸肌和膝关节屈肌。大腿肌肉的T2加权磁共振成像(MRI)将用于监测每个强度水平的肌肉损伤证据，并确定安全的运动范围。其他安全措施包括言语疼痛模拟量表、临床检查和血清肌酸激酶(CK)水平。在目标2中，我们将实施一项试点干预研究，以检查12岁以下儿童的可行性和安全性 DMD儿童的一周家庭等长强化计划。在这项研究中，10名患有DMD的男孩将使用目标1中确定的参数和剂量完成一项渐进运动计划。在整个研究过程中，将定期进行强度和安全性评估。10名没有参加运动干预的患有DMD的男孩将以类似的时间间隔进行测试，并作为对照组。这项先导性研究的数据将用于进行所需的能量分析，以设计一项适当的临床干预研究。这一创新的应用程序可能会对公共卫生产生重大影响，因为它为 DMD患者运动参数指南的制定。

DESCRIPTION (provided by applicant): Duchenne muscular dystrophy (DMD) is a debilitating neuromuscular disease that causes muscle breakdown, weakness, and eventual death. Over the last 40 years parents have received little guidance on the potential of exercise as a therapeutic strategy to maintain muscle function. It is well known that high intensity exercise and eccentric contractions can result in muscle damage in dystrophic muscle, yet the absence of muscle loading will conversely result in muscle wasting. Recent research in rodent models and milder forms of muscular dystrophy supports earlier studies that resistance exercise may have beneficial effects for maintenance of muscle mass in dystrophic muscle. However, careful and systematic investigation into the safety and feasibility of resistance exercise is needed to consider its implementation in boys with DMD. The overall objective of this pilot study is to assess whether a mild to moderate-intensity strengthening exercise program can be safely implemented in boys with DMD. In Aim 1 we will determine the dose response and safety of mild to moderate-intensity isometric resistance exercise in children with DMD. Twelve ambulatory boys with DMD will participate in an isometric exercise dosing protocol, in which the load is progressively increased. In this early proof of concept pilot study, two large muscle groups will be studied: the knee extensors and the knee flexors. T2 weighted magnetic resonance imaging (MRI) of the thigh muscles will be used to monitor evidence of muscle damage at each intensity level and determine a safe exercise range. Other safety measures will include a verbal pain analog scale, clinical examination, and serum creatine kinase (CK) levels. In Aim 2 we will implement a pilot intervention study to examine the feasibility and safety of a 12 week in-home isometric strengthening program in children with DMD. In this study, 10 boys with DMD will complete a progressive exercise program using the parameters and dose identified in Aim 1. Assessment of strength and safety will be performed at regular time intervals throughout the study. Ten boys with DMD not participating in an exercise intervention will be tested at similar time intervals and serve as controls. The data from this pilot study will serve to perform the power analysis needed to design an appropriately powered clinical intervention study. This innovative application may have significant public health implications as it sets the stage for the development of guidelines for exercise parameters in patients with DMD.