Development of a rapid diagnostic assay for Myasthenia Gravis

重症肌无力快速诊断检测方法的开发

• 批准号: 9909271
• 负责人: LANCE P FORD
• 金额: $ 22.5万
• 依托单位: ATTOGENE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909271
• 关键词: Algae; Amputees; Anatoxins; Antibodies; Autoantibodies; Binding; Biohazardous Substance; Biological Assay; Blurred vision; Breathing; Cell Line; Cell membrane; Cells; Cholinergic Receptors; Cholinesterase Inhibitors; Clinical; Cone; Consumption; Cyclic GMP; Decision Making; Deglutition; Detection; Development; Devices; Diagnosis; Diagnostic tests; Diplopia; Disease; Disease Progression; Early Diagnosis; Equipment; Ethics; Exposure to; Eye; Facial Expression; Fc Receptor; Food Safety; Goals; Gold Colloid; Hazardous Substances; Health; Human; Immunodominant Epitopes; Immunosuppressive Agents; Impairment; Individual; Industry; Intravenous Immunoglobulins; Label; Laboratory Personnel; Lateral; Life; Marines; Medical; Membrane; Methodology; Methods; Monitor; Motor Endplate; Muscle; Muscle Fatigue; Muscle Weakness; Muscle function; Myasthenia Gravis; Neurotoxins; Nicotinic Receptors; Pathologist; Patients; Penetration; Peptides; Performance; Pharmaceutical Preparations; Phase; Physicians; Physiological; Plasmapheresis; Preparation; Price; Production; Property; Quality of life; Radioactive; Rattus; Reagent; Rhabdomyosarcoma; Sampling; Savings; Secure; Sensitivity and Specificity; Shortness of Breath; Snails; Snakes; Source; Speech; Speed; Symptoms; Technology; Test Result; Testing; Thymectomy; Time; Toxin; Toxin Conjugates; Translating; Ventilator; Visual; anti-IgG; associated symptom; clinical Diagnosis; commercial application; common symptom; cost; diagnostic assay; follow-up; gymnodimine; improved; instrumentation; limb amputation; nanobodies; novel; phase 2 study; prototype; rapid detection; receptor; receptor binding; screening; treatment response; user-friendly

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.

项目总结/摘要 自身抗体结合运动终板连接烟碱乙酰胆碱的生理效应 乙酰胆碱受体（AchR）引起许多与重症肌无力（MG）相关的症状， 单眼或双眼下垂，视力模糊或复视，面部表情变化，吞咽困难， 呼吸急促、言语障碍和肌肉功能虚弱。在某些情况下，危机可能发生在 控制呼吸的肌肉减弱到需要呼吸机的程度。的 可以通过胸腺切除术，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。虽然这可能是一个威胁生命和严重 衰弱性疾病，MG临床诊断往往被忽视，因为肌肉疲劳是常见的 许多其他疾病的症状和大多数症状直到AchR显着丢失才被发现 （正常水平的约30%），因此早期检测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是 并且通常依赖于放射性标记的毒素缀合物、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测定配置，用于快速和灵敏地检测抗AchR。我们的目标是 将放射性抗AchR受体结合测定转化为快速、用户友好和稳健的可视化， 检测方法我们期望该测定将具有重要的商业应用，因为它将 操作简单、成本低、稳健，并且预期对于监测抗AchR和可能的抗AchR抗体是有价值的。 其他重要化合物的大光谱。我们提出的方法将导致大量的成本和时间 节约改进。这将使整个医疗行业的测试范围更广，响应速度更快 接受治疗这些优势将是一个显着的改善那些诊断为MG。