Department of Neuroscience, Institute for Experimental Medical Research (DETAE), Istanbul University, Istanbul, Turkey.
INSERM U974, Paris, France; CNRS UMR 7215, Paris, France; UPMC Univ Paris 6, Paris, France; AIM, Institute of Myology, Paris, France.
Exp Neurol. 2015 Aug;270:11-7. doi: 10.1016/j.expneurol.2015.02.009. Epub 2015 Feb 16.
Myasthenia gravis (MG) is an autoimmune disorder characterized by generalized muscle weakness due to neuromuscular junction (NMJ) dysfunction brought by acetylcholine receptor (AChR) antibodies in most cases. Although steroids and other immunosuppressants are effectively used for treatment of MG, these medications often cause severe side effects and a complete remission cannot be obtained in many cases. For pre-clinical evaluation of more effective and less toxic treatment methods for MG, the experimental autoimmune myasthenia gravis (EAMG) induced by Torpedo AChR immunization has become one of the standard animal models. Although numerous compounds have been recently proposed for MG mostly by using the active immunization EAMG model, only a few have been proven to be effective in MG patients. The variability in the experimental design, immunization methods and outcome measurements of pre-clinical EAMG studies make it difficult to interpret the published reports and assess the potential for application to MG patients. In an effort to standardize the active immunization EAMG model, we propose standard procedures for animal care conditions, sampling and randomization of mice, experimental design and outcome measures. Utilization of these standard procedures might improve the power of pre-clinical EAMG experiments and increase the chances for identifying promising novel treatment methods that can be effectively translated into clinical trials for MG.
重症肌无力(MG)是一种自身免疫性疾病,其特征是由于大多数情况下乙酰胆碱受体(AChR)抗体引起的神经肌肉接头(NMJ)功能障碍而导致全身肌肉无力。虽然类固醇和其他免疫抑制剂有效地用于治疗 MG,但这些药物经常会引起严重的副作用,并且在许多情况下无法获得完全缓解。为了对 MG 的更有效和毒性更小的治疗方法进行临床前评估,使用电鳗 AChR 免疫接种诱导的实验性自身免疫性重症肌无力(EAMG)已成为标准动物模型之一。尽管最近有许多化合物被提议用于 MG,主要是通过使用主动免疫 EAMG 模型,但只有少数已被证明对 MG 患者有效。临床前 EAMG 研究的实验设计、免疫接种方法和结果测量的可变性使得难以解释已发表的报告并评估将其应用于 MG 患者的潜力。为了标准化主动免疫 EAMG 模型,我们提出了动物护理条件、小鼠采样和随机分组、实验设计和结果测量的标准程序。利用这些标准程序可能会提高临床前 EAMG 实验的效能,并增加识别有前途的新型治疗方法的机会,这些方法可以有效地转化为 MG 的临床试验。