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: 10493361
• 负责人: Woon-Hong Yeo
• 金额: $ 19.71万
• 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/10493361
• 关键词: Age; American; Animal Model; Animals; Barium; Choking; Clinical Research; Contrast Media; Coughing; Data; Deglutition; Deglutition Disorders; Dehydration; Detection; Development; Devices; Diagnosis; 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; X-Ray Medical Imaging; 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; wireless

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.

项目概要 吞咽困难是吞咽反射的神经和肌肉功能受损， 导致令人衰弱甚至可能致命的病症，例如窒息、营养不良、脱水 或吞咽时肺炎。吞咽困难困扰着近 1500 万美国人，尤其是 50-60 岁或以上的人出现吞咽困难的可能性高达 20%。然而，无论 吞咽困难的原因，目前尚无可用的治疗方法。限制 研究吞咽困难的临床前工具和方法是缺乏研究的最大原因之一 吞咽困难的治疗。电视透视吞咽研究 (VFSS) 用于临床研究以及药物动物模型研究中诊断吞咽困难 发展。然而，临床研究中的VFSS方法依赖于患者的积极配合。 人类受试者，例如摄入含有钡的食物（口服造影剂）和运动 X 射线成像期间的固定。 VFSS 工具显示了动物研究中的严重问题 由于目标不可控，导致图像质量差、药物不可靠 发展。总体而言，现有的商业系统都无法提供便携式、实时、 持续监测人类或动物的吞咽情况。 在这里，该项目将开发一种新颖的纳米膜电子系统，该系统提供 以非侵入性方式对皮肤上的吞咽活动进行连续、定量的评估 大鼠模型，这将有助于开发潜在的吞咽困难药物。具体来说，我们将开发 柔软、超薄、轻量、微型可穿戴电子设备，用于监测随时间变化的变化 通过无线实时记录肌电图来评估吞咽肌肉功能 吞咽困难大鼠模型的吞咽肌肉。在这个项目中，我们初步研究了评估 吞咽困难治疗将重点关注 ALS 相关的吞咽困难，因为有成熟的治疗方法 幼年时患有严重吞咽困难的动物模型（转基因超氧化物歧化酶；SODG93A） 年龄。 SODG93A动物模型已被广泛用于筛选潜在的治疗药物 化合物，包括 FDA 批准的两种 ALS 药物：依达拉奉和利鲁唑。总的来说，如果 如果成功，新开发的纳米膜电子器件将改变游戏规则 针对 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。该研究成果有望为有效治疗提供新药 吞咽困难的治疗，最终将降低死亡率并提高生活质量 吞咽困难患者。