Development of Nanomembrane Electronics and Machine-Learning Algorithms for Quantitative Screening of Dysphagia Therapeutics

开发用于定量筛选吞咽困难治疗药物的纳米膜电子学和机器学习算法

• 批准号: 10373326
• 负责人: Woon-Hong Yeo
• 金额: $ 21.19万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-23 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373326
• 关键词: Age; American; Animal Model; Animals; Barium; Choking; Clinical Research; Contrast Media; Coughing; Data; Deglutition; Deglutition Disorders; Dehydration; Detection; Development; Devices; Diagnosis; Diagnostic radiologic examination; Disease; Drug Evaluation; Electronics; Evaluation; Experimental Designs; FDA approved; Food; Guidelines; Human; Image; Immobilization; Impairment; Individual; Ingestion; Malnutrition; Mastication; Measurement; Mechanics; Methods; Modeling; Monitor; Movement; Muscle; Muscle function; Neurologic; Oral; Outcomes Research; Patients; Performance; Pharmaceutical Preparations; Pneumonia; Quality of life; Rattus; Reflex action; Research; Riluzole; Signal Transduction; Skin; Stretching; Superoxide Dismutase; System; Systems Integration; Testing; Therapeutic; Time; Transgenic Organisms; Wireless Technology; base; classification algorithm; computerized data processing; deep learning; deep learning algorithm; design; digital; drug candidate; drug classification; drug development; drug efficacy; effective therapy; efficacy evaluation; flexibility; human subject; improved; in vivo; light weight; machine learning algorithm; miniaturize; mortality; nanomembrane; novel; novel therapeutics; phenylmethylpyrazolone; portability; pre-clinical; screening; signal processing; therapeutic evaluation; tool; wearable device; wearable sensor technology

Project Summary Dysphagia is an impairment of the swallow reflex's neurological and muscular functions that causes a debilitating and potentially deadly condition such as choking, malnutrition, dehydration or pneumonia during swallowing. Dysphagia afflicts almost 15 million Americans, particularly individuals 50-60 years or older with up to a 20% chance of dysphagia. However, regardless of the cause of dysphagia, currently there are no available therapeutic treatments. Limitation of preclinical tools and methods to study dysphagia is one of the biggest reasons for the lack of therapeutic treatment for dysphagia. Video-fluoroscopic swallowing study (VFSS) has been used to diagnose dysphagia in a clinical study as well as research with animal models for drug development. However, the VFSS method in clinical study relies on the active cooperation of a human subject, such as ingestion of food with barium (oral contrast agent) and movement immobilization during X-ray imaging. The VFSS tool shows the severe issue in an animal study due to uncontrollable target, which results in poor image quality and unreliable drug development. Overall, none of the existing commercial systems can offer a portable, real-time, continuous monitoring of swallowing with either humans or animals. Here, this project will develop a novel, nanomembrane electronic system that offers a continuous, quantitative assessment of swallowing activities in a non-invasive way on the skin of rat models, which will help to develop potential dysphagia drugs. Specifically, we will develop soft, ultrathin, lightweight, miniaturized wearable electronics to monitor time-dependent changes of swallowing muscle functions via wireless, real-time recording of electromyograms on swallowing muscles of a dysphagia rat model. In this project, our initial study in the evaluation of dysphagia therapeutics will focus on ALS-related dysphagia since there are well-established animal models (transgenic superoxide dismutase; SODG93A) with severe dysphagia at a young age. SODG93A animal models have been widely used to screen potential therapeutic compounds, including two FDA-approved ALS drugs: edaravone and riluzole. Collectively, if successful, the newly developed nanomembrane electronics will be a game-changer in the therapeutic evaluation of candidate drugs for ALS-related dysphagia as well as other diseases- related dysphagia. The research outcome is expected to provide a new drug for an effective treatment of dysphagia, which will eventually reduce mortality and improve the quality of life of dysphagia patients.

项目摘要 吞咽困难是燕子反射的神经和肌肉功能的损害 引起令人衰弱的致命状况，例如窒息，营养不良，脱水 或吞咽过程中的肺炎。吞咽困难遭受了近1500万美国人的困扰，尤其是 50 - 60年以上的个人患有吞咽困难的机会20％。但是，无论如何 吞咽困难的原因，目前尚无可用的治疗疗法。限制 研究吞咽困难的临床前工具和方法是缺乏的最大原因之一 吞咽困难的治疗治疗。视频氟镜吞咽研究（VFSS）已经 用于在临床研究中诊断吞咽困难以及药物动物模型的研究 发展。但是，临床研究中的VFSS方法依赖于A的积极合作 人类受试者，例如用钡（口服造影剂）和运动摄入食物 X射线成像过程中的固定化。 VFSS工具在动物研究中显示了严重的问题 由于无法控制的目标，这会导致图像质量差和不可靠的药物 发展。总体而言，现有的商业系统都无法提供便携式，实时的 连续监测人类或动物的吞咽。 在这里，该项目将开发出一种小说的纳米膜电子系统，该系统提供 对吞咽活动的连续定量评估以非侵入性的方式在皮肤上 大鼠模型将有助于开发潜在的吞咽困难药物。具体来说，我们将发展 柔软，超薄，轻巧，微型可穿戴电子设备，以监视时间依赖性变化 吞咽肌肉功能通过无线，实时记录肌电图的实时记录 吞咽吞咽困难大鼠模型的肌肉。在这个项目中，我们在评估中的最初研究 吞咽困难将重点放在与ALS相关的吞咽困境上 动物模型（转基因超氧化物歧化酶； SODG93A）在年轻人处有严重的吞咽困难 年龄。 SODG93A动物模型已被广泛用于筛选潜在的治疗性 化合物，包括两种FDA批准的ALS药物：Edaravone和Riluzole。集体，如果 成功，新开发的纳米膜电子设备将成为改变游戏的人 对ALS相关吞咽困难以及其他疾病的候选药物的治疗评估 相关吞咽困难。预计研究结果将为有效提供新药 吞咽困难的治疗，最终将降低死亡率并改善生活质量 吞咽困难患者。