Mesh : Amyotrophic Lateral Sclerosis / physiopathology drug therapy Animals Disease Models, Animal Wearable Electronic Devices Electromyography / methods Drug Evaluation, Preclinical Deglutition Disorders / physiopathology etiology Muscle, Skeletal / drug effects physiopathology innervation Humans Male Motor Neurons / drug effects physiology Rats

来  源:   DOI:10.1038/s41467-024-51300-1   PDF(Pubmed)

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FDA批准的药物是通过监测肌萎缩性侧索硬化症模型动物的肢体肌肉功能和组织学分析而产生的。由于传统临床前工具的局限性:过度使用动物和疾病进展的离散检测,该疾病的候选药物尚未进行球发作型测试。这里,我们的研究引入了一体化,无线,集成的可穿戴系统,用于在自然进食行为期间促进动物吞咽困难相关肌肉的连续药物疗效评估。通过结合基于kirigami的应变隔离机制,这种安装在动物皮肤上的装置减轻了由不可预测的动物运动引起的肌电图信号污染。我们的发现表明这个系统,测量运动神经元神经支配的进展,提供高精度监测药物对吞咽困难负责的延髓肌肉的影响。这项研究为开发退行性神经肌肉疾病的治疗解决方案的更人性化和有效的方法铺平了道路。
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