Sikorski Patricia M, Kusner Linda L
Department of Pharmacology and Physiology, Department of Neurology, George Washington University, Washington, DC, United States.
Department of Pharmacology and Physiology, Department of Neurology, George Washington University, Washington, DC, United States.
Int Rev Neurobiol. 2025;182:145-160. doi: 10.1016/bs.irn.2025.04.029. Epub 2025 Jul 9.
Animal models offer a platform to advance our understanding of myasthenia gravis (MG), an autoimmune disorder characterized by impaired neuromuscular transmission. Experimental autoimmune MG models (EAMG) actively induce autoimmunity through antigen immunization, aiding in understanding the immune response to self. Passive transfer models (PTMG) involve the injection of pathogenic antibodies into animals, providing insights into antibody-mediated mechanisms and complement-driven damage to the neuromuscular junction (NMJ). The pathogenic effect of autoantibodies targeting acetylcholine receptors (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (Lrp4) results in changes to the NMJ that are mechanistically distinct. These models validate therapeutic interventions preclinically, with methodologies ranging from antibody transfer to genetic modifications. Despite the translational challenges, these models bridge preclinical research and clinical applications, enabling the development of targeted treatments for MG.
动物模型为增进我们对重症肌无力（MG）的理解提供了一个平台，重症肌无力是一种以神经肌肉传递受损为特征的自身免疫性疾病。实验性自身免疫性重症肌无力模型（EAMG）通过抗原免疫主动诱导自身免疫，有助于理解对自身的免疫反应。被动转移模型（PTMG）涉及将致病性抗体注射到动物体内，从而深入了解抗体介导的机制以及补体驱动的对神经肌肉接头（NMJ）的损伤。靶向乙酰胆碱受体（AChR）、肌肉特异性激酶（MuSK）和低密度脂蛋白受体相关蛋白4（Lrp4）的自身抗体的致病作用导致神经肌肉接头发生机制上不同的变化。这些模型在临床前验证治疗干预措施，方法包括抗体转移到基因修饰。尽管存在转化方面的挑战，但这些模型架起了临床前研究和临床应用之间的桥梁，推动了针对重症肌无力的靶向治疗的发展。
