't Hart Bert A, Massacesi Luca
Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
J Neuropathol Exp Neurol. 2009 Apr;68(4):341-55. doi: 10.1097/NEN.0b013e31819f1d24.
The efficacy of many new immunomodulatory therapies for multiple sclerosis (MS) patients has often been disappointing, reflecting our incomplete understanding of this enigmatic disease. There is a growing awareness that, at least in part, there may be limited applicability to the human disease of results obtained in the widely studied MS model experimental autoimmune encephalomyelitis in rodents. This review describes the experimental autoimmune encephalomyelitis model developed in a small neotropical primate, the common marmoset (Callithrix jacchus). The model has features including clinicopathologic correlation patterns, lesion heterogeneity, immunologic mechanisms, and disease markers that more closely mimic the human disease. Several unique features of experimental autoimmune encephalomyelitis in marmosets, together with their outbred nature and close genetic and immunologic similarities to humans, create an attractive experimental model for translational research into MS, particularly for the preclinical evaluation of new biologic therapeutic molecules that cannot be investigated in rodents because of their species specificity. Moreover, this model provides new insights into possible pathogenetic mechanisms in MS.
许多针对多发性硬化症(MS)患者的新型免疫调节疗法的疗效常常令人失望,这反映出我们对这种神秘疾病的理解并不完整。人们越来越意识到,至少在一定程度上,在广泛研究的啮齿动物实验性自身免疫性脑脊髓炎(EAE)模型中获得的结果,对人类疾病的适用性可能有限。本综述描述了在一种小型新热带灵长类动物——普通狨猴(Callithrix jacchus)中建立的实验性自身免疫性脑脊髓炎模型。该模型具有临床病理相关模式、病变异质性、免疫机制和疾病标志物等特征,能更紧密地模拟人类疾病。狨猴实验性自身免疫性脑脊髓炎的几个独特特征,连同它们的远交性质以及与人类在遗传和免疫方面的密切相似性,为MS的转化研究创造了一个有吸引力的实验模型,特别是对于那些因物种特异性而无法在啮齿动物中研究的新型生物治疗分子的临床前评估。此外,该模型为MS可能的发病机制提供了新的见解。