Wearable Sensors for Quantitative Assessment of Motor Impairment in Huntington's Disease

摘要 亨廷顿病(HD)运动功能障碍的主要测量方法是统一的亨廷顿氏 疾病评定量表(UHDRS)：运动总评分，具有主观性和概括性。可穿戴传感器可以 能够客观、敏感、持续地评估患有各种运动障碍的个人的运动障碍 神经运动障碍。这一点很重要，因为大量的客观数据是以较高的 真实世界环境中的频率可以减少早期临床试验的时间和成本。在临床上， 在日常生活活动中用于运动评估的可穿戴传感器可以用来加速和改进 药物滴定。在高清中，可穿戴的传感器可以检测预装清单中细微的运动异常 疾病阶段对于监测早期治疗干预试验将是有价值的，并可以提供 洞察临床疾病的发病阶段。 我们最近完成了一系列初步研究(1篇已发表的文章和1篇准备中的手稿) 由Auspex制药公司(现在是Teva制药公司的一部分)支持，展示了一款可穿戴设备 躯干上的传感器可以检测HD患者的步态相关运动障碍，手腕上的可穿戴传感器可以 确定上肢舞蹈症的发生和严重程度。在此直接到第二阶段SBIR中，我们建议 在第一阶段相当于试点工作的基础上，开发用于连续远程的远程医疗系统 使用可穿戴传感器评估亨廷顿舞蹈症。根据我们的初步研究，我们建议 开发一个由两个可穿戴传感器组成的系统，这些传感器可以佩戴在主导手腕和躯干上。 我们将与罗切斯特大学合作，进行一项临床研究，以改进和进一步验证 用于检测舞蹈症严重性的算法，并评估传感器派生的测量是否可以检测到 症状前期抗舞蹈病药物或细微运动异常的药理学反应 高清。参与者将在基线时到诊所就诊，然后每季度就诊一次，总共就诊5次。评估将 包括UHDRS的运动部分，Q运动评估，计时步行测试，以及一系列 日常生活的模拟活动。这项评估将进行两次，服药前和服药后。 参与者将在门诊评估期间以及之后的一周内佩戴这两个传感器。 这项拟议的技术有很大的商业化潜力。这包括药品 临床试验，可穿戴传感器的前景导致了对开发的重大投资 治疗帕金森氏症的技术。然而，亨廷顿氏症患者人数较少 疾病已经完全被忽视了。这既代表了重大的公共卫生需求，也代表了市场 生物传感的机遇。为我们的第一阶段提供资金支持的Teva制药公司 同等的试点工作，以及美国亨廷顿病学会已经表达了对 建议的技术，并支持我们的努力(见支持函)。

ABSTRACT The principal means of measuring motor impairment in Huntington disease (HD) is the Unified Huntington's Disease Rating Scale (UHDRS) total motor score, which is subjective and categorical. Wearable sensors could enable objective, sensitive, continuous assessment of motor impairments in individuals with a variety of neurological movement disorders. This is important because large amounts of objective data acquired at a high frequency in a real-world setting could reduce the time and cost of early stage clinical trials. Clinically, wearable sensors for motor assessment during activities of daily living could be used to expedite and improve medication titration. In HD, wearable sensors that could detect subtle motor abnormalities in the premanifest phase of the disease would be valuable for monitoring early therapeutic intervention trials and could provide insight into the phase of clinical disease onset. We have recently completed a series of pilot studies (1 published article and 1 manuscript in preparation) supported by Auspex Pharmaceuticals (now part of Teva Pharmaceuticals) demonstrating that a wearable sensor on the torso can detect gait related motor impairments in HD and a wearable sensor on the wrist can identify the occurrence and severity of upper extremity chorea. In this Direct to Phase II SBIR we propose to build upon this Phase I equivalent pilot work by developing a telehealth system for continuous remote assessment of Huntington's chorea using wearable sensors. Based on our pilot research we propose to develop a system consisting of two wearables sensors to be worn on the dominant wrist and on the torso. In partnership with the University of Rochester, we will conduct a clinical study to improve and further validate algorithms for detecting chorea severity, and to evaluate whether sensor-derived measures can detect pharmacological response to anti-chorea medication or subtle motor abnormalities in the premanifest stage of HD. Participants will visit the clinic at baseline and then once a quarter for a total of 5 visits. Assessments will include the motor portion of the UHDRS, Q-motor assessment, a Timed-Up-and-Go walking test, and a series of simulated activities of daily living. This assessment will be conducted twice, on- and off-medication. Participants will wear the two sensors during in-clinic assessments and for a period of 1-week thereafter. There is a significant commercialization potential for the proposed technology. This includes pharmaceutical clinical trials, where the promise of wearable sensors has led to significant investment in the development of technologies for Parkinson's disease. However, the smaller patient population of individuals with Huntington's disease has been completely overlooked. This represents both a significant public health need and market opportunity for BioSensics. Teva Pharmaceuticals, who provided the financial support for our Phase I equivalent pilot work, and the Huntington's Disease Society of America have expressed an interest in the proposed technology and are supportive of our efforts (see Letters of Support).