Development of a rapid diagnostic assay for Myasthenia Gravis

项目摘要/摘要 自身抗体与运动终板接头烟碱型乙酰胆碱结合的生理效应 受体(ACHR)引起与重症肌无力(MG)相关的多种症状，其特征是 一只或两只眼睛下垂，视力模糊或复视，面部表情改变，吞咽困难， 呼吸急促，言语障碍，肌肉功能虚弱。在某些情况下，危机可能发生在 控制呼吸的肌肉会减弱到需要呼吸机的程度。这个 疾病可以通过胸腺切除、使用抗胆碱酯酶药物、免疫抑制药物、 血浆置换和静脉注射免疫球蛋白。尽管这可能会危及生命，并严重 衰弱疾病，MG临床诊断经常被忽视，因为肌肉疲劳是一种常见的 许多其他疾病的症状和大多数症状直到ACHR显著丧失时才能被发现 (∼是正常水平的30%)，因此，及早发现将是一个明显的优势。 在大多数MG患者中发现的用于检测抗AchR抗体的受体结合试验有 耗时且通常依赖于放射性标记的毒素结合物，昂贵的设备和 先进的检测技术，需要高技能的劳动力。这项建议的目的是 开发一种新的侧向流动分析装置，用于快速、灵敏地检测抗AchR。我们的目标是 将放射性抗AchR受体结合试验转换为快速、用户友好和健壮的可视化 检测方法。我们预计这种分析方法将有重大的商业应用，因为它将 操作简单、成本低、健壮，有望在监测抗AchR和可能的 其他重要化合物的大光谱。我们提出的方法将导致巨大的成本和时间 节省改进。这将在整个医疗行业实现更广泛的测试和更快的响应 接受治疗。对于那些被诊断为MG的人来说，这些优势将是一个显著的进步。

Project Summary/Abstract The physiological effect of autoantibody binding to the motor endplate junction nicotinic acetylcholine receptors (AchR) causes numerous symptoms associated with Myasthenia Gravis (MG) and is characterized by drooping of one or both eyes, blurred or double vision, change in facial expression, difficulty swallowing, shortness of breath, impaired speech and weakness of muscle function. In some cases, a crisis can occur in which the muscles that control breathing weaken to the point where individuals require a ventilator. The disease can be treated by thymectomy, use of anticholinesterase medications, immunosuppressive drugs, plasmapheresis and intravenous immunoglobulin. Although this can be a life threatening and severely debilitating disease, MG clinical diagnosis often goes overlooked because muscles fatigue is a common symptom of many other disorders and most symptoms are not identified until there is a significant loss in AchR (∼30% of normal levels) thus earlier detection would be a clear advantage. The receptor binding assays for the detection of anti-AchR antibody found in the majority of MG patients are time consuming and typically rely on radioactively labeled toxin conjugate, expensive equipment and sophisticated detection technologies that require a highly skilled workforce. The objective of this proposal is to develop a novel lateral flow assay configuration for the rapid and sensitive detection of Anti-AchR. Our goal is to convert the radioactive anti-AchR receptor binding assays into a rapid, user-friendly and robust visual detection methodology. We expect that this assay will have significant commercial applications because it will be simple to perform, low cost, robust and is expected to be valuable for monitoring anti-AchR and possibly a large spectrum of other important compounds. The approach we propose will lead to significant cost and time saving improvements. This will enable broader testing throughout the medical industry and faster responses for treatment. These advantages would be a significant improvement for those diagnosed with MG.