Development of a rapid diagnostic assay for Myasthenia Gravis

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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.