Forced Exercise: A New Therapy for the Treatment of Parkinson's Disease

描述（由申请人提供）：由Alberts和团队（Cleveland Clinic）进行的一项小型试点研究表明，持续的强制运动（FE）可能与药物或手术植入微电极进行深部脑刺激一样或更有效地改善帕金森病（PD）患者的运动功能。在体育锻炼中，一个人积极锻炼的速度超过了他（她）自己身体上能够达到和维持的速度。在Alberts的研究中，患者每周完成三次40分钟的FE训练，持续8周，使用固定双人自行车，“教练”提供约75%的能量来维持80-90转/分钟的节奏，患者提供足够的能量来维持目标心率的80%。令人惊讶的是，这种疗法改善了上半身和下半身的运动功能。不幸的是，这种FE方案的商业化将是非常昂贵的，需要一个健康的教练坐在固定双人组的前座上，并需要一个监督员来确保达到并保持目标FE水平。RSS Industries, Inc.提议设计、制造和台架测试一种机动运动自行车原型，Theracycle PD的性能，能够取代Alberts的FE方案中教练提供的物理输入。这项研究的起点将是现有的Theracycle，这是一种由RSS开发和制造的固定的、软件控制的马达驱动的治疗性运动系统，于2002年推出，供有严重身体残疾的个人使用。在为期一年的SBIR第一阶段工作计划中实施的创新和增强将使原型Theracycle PD能够：1)允许骑手通过超速驱动电机实现FE；2)使用骑手的心率作为控制回路的一部分，以表明何时需要更多的蹬车努力来维持目标心率（和FE），以及何时电机可以提供这种努力。具体目标（SAs）包括：替换现有的齿轮箱上的标准Theracycle与向后驱动，低阻力传动系统。开发和集成一个心率监测器，电子元件，增强的GUI和必要的软件。SA 3：构建并释放测试3个额外的Theracycle PD原型单元，用于SBIR II期FE方案的临床疗效测试（总共4个单元，2个临床站点各1个主要和1个备用）。可行性/进展标准：Theracycle PD原型在FE期间达到的心率和踏板节奏值必须在Alberts试点研究中报告的值范围的10%以内。不试图确定FE方案的有效性，因为这将在SBIR第二期中解决。

DESCRIPTION (provided by applicant): A small pilot study by Alberts and team (Cleveland Clinic) suggests that sustained forced exercise (FE) may be as or more effective than medication or surgical implantation of microelectrodes for deep brain stimulation in improving motor function in individuals with Parkinson's disease (PD). In FE, an individual actively exercises at a rate in excess of that which (s)he is physically able to attain and maintain by (her)himself. In the Alberts' study, patients completed three 40 min FE sessions/week for 8 weeks, using a stationary tandem bicycle on which a "trainer" provided ~75% of the energy required to maintain a cadence of 80-90 rpm and the patient provided sufficient energy to maintain a target heart rate 80% of maximum for their age. Somewhat surprisingly, this regimen improved upper as well as lower body motor function. Unfortunately, commercialization of this FE regimen would be prohibitively expensive, requiring a healthy trainer to man the front seat of the stationary tandem and a supervisor to insure the targeted level of FE was reached and maintained. RSS Industries, Inc. proposes to design, build and bench test the performance of a motorized exercise cycle prototype, the Theracycle PD, able to replace the physical input provided by the trainer in the Alberts' FE regimen. The starting point will be the existing Theracycle, a stationary, software-controlled motor driven therapeutic exercise system developed and manufactured by RSS and launched in 2002 for use by individuals with significant physical disabilities. Innovations and enhancements to be implemented during the 1 year SBIR Phase I work plan will enable the prototype Theracycle PD to: 1) allow the rider to achieve FE by overdriving the motor; and 2) use the rider's heart rate as part of a control loop to signal when more pedaling effort is required to maintain target heart rate (and FE) and when the motor can provide the effort. Specific aims (SAs) include: SA1. Replace existing gear box on a standard Theracycle with a back-drivable, low resistance gearing system. SA 2: Develop and integrate a heart rate monitor, electronic components, enhanced GUI and requisite soft- ware. SA 3: Build and release test 3 additional prototype Theracycle PD units for use in clinical efficacy testing of FE regimens in SBIR Phase II (4 units total; 1 primary and 1 backup for each of 2 clinical sites). Feasibility/Progression Criteria: The heart rate and pedal cadence values achieved during the FE period on the Theracycle PD prototypes must be within 10% of the range of values reported in the Alberts' pilot study. No attempt will be made to ascertain effectiveness of the FE regimen as that will be addressed in SBIR Phase II. PUBLIC HEALTH RELEVANCE: Individuals with Parkinson's disease (PD) suffer progressive loss of upper and lower body motor functions, for which drug therapy becomes less and less effective over time. A recent pilot study suggests that forced exercise on a tandem bicycle (in which a second rider aids in pedaling at a rate well above that achievable by a PD patient's voluntary effort) can produce whole body improvements in motor function at least as good as and possibly better than those achieved by medication in patients with advanced disease. The work proposed here is designed to create the Theracycle PD, a stationary exercise cycle using a motor to replace the physical effort provided by the second rider, with the long term goal of making forced exercise an affordable (<$5000) option available to a much wider group of PD patients.