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基于肌萎缩侧索硬化症动物模型的一体化可穿戴药物疗效评估系统,用于球部肌肉功能研究。

All-in-one wearable drug efficacy assessment systems for bulbar muscle function using amyotrophic lateral sclerosis animal models.

机构信息

Wearable Intelligent Systems and Healthcare Center (WISH Center) at the Institute for Matter and Systems, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, 30332, USA.

出版信息

Nat Commun. 2024 Aug 9;15(1):6803. doi: 10.1038/s41467-024-51300-1.

Abstract

Preclinical studies are crucial for developing amyotrophic lateral sclerosis drugs. Current FDA-approved drugs have been created by monitoring limb muscle function and histological analysis of amyotrophic lateral sclerosis model animals. Drug candidates for this disease have yet to be tested for bulbar-onset type due to the limitations of traditional preclinical tools: excessive animal use and discrete detection of disease progress. Here, our study introduces an all-in-one, wireless, integrated wearable system for facilitating continuous drug efficacy assessment of dysphagia-related muscles in animals during natural eating behaviors. By incorporating a kirigami-based strain-isolation mechanism, this device mounted on the skin of animals mitigates electromyography signal contamination caused by unpredictable animal movements. Our findings indicate this system, measuring the progression of motor neuron denervation, offers high precision in monitoring drug effects on dysphagia-responsible bulbar muscles. This study paves the way for more humane and efficient approaches to developing treatment solutions for degenerative neuromuscular diseases.

摘要

临床前研究对于开发肌萎缩侧索硬化症药物至关重要。目前,美国食品和药物管理局批准的药物是通过监测肢体肌肉功能和肌萎缩侧索硬化症模型动物的组织学分析来开发的。由于传统临床前工具的局限性,尚未对延髓发病型的候选药物进行测试:动物使用过度,且离散检测疾病进展。在这里,我们的研究引入了一种一体化、无线、集成的可穿戴系统,用于在自然进食行为中促进对动物与吞咽相关肌肉的药物疗效的连续评估。通过结合基于剪纸的应变隔离机制,该装置安装在动物皮肤上,可以减轻由不可预测的动物运动引起的肌电图信号污染。我们的研究结果表明,该系统测量运动神经元去神经支配的进展,在监测吞咽相关延髓肌肉药物效应方面具有高精度。这项研究为开发退行性神经肌肉疾病的治疗方法开辟了更人性化和更有效的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b5b/11315987/e5c3ab279acd/41467_2024_51300_Fig1_HTML.jpg

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