多发性硬化
实验性自身免疫性脑脊髓炎
免疫疗法
基因工程
人性化鼠标
自身免疫
免疫学
临床试验
动物模型
医学
CD8型
神经科学
生物
计算生物学
生物信息学
免疫系统
基因
遗传学
内分泌学
作者
Bert A. ’t Hart,Bruno Gran,Robert Weissert
标识
DOI:10.1016/j.molmed.2010.11.006
摘要
The high failure rate of immunotherapies in multiple sclerosis (MS) clinical trials demonstrates problems in translating new treatment concepts from animal models to the patient. One main reason for this 'immunotherapy gap' is the usage of immunologically immature, microbiologically clean and genetically homogeneous rodent strains. Another reason is the artificial nature of the experimental autoimmune encephalomyelitis model, which favors CD4+ T cell driven autoimmune mechanisms, whereas CD8+ T cells are prevalent in MS lesions. In this paper, we discuss preclinical models in humanized rodents and non-human primates that are genetically closer to MS. We also discuss models that best reproduce specific aspects of MS pathology and how these can potentially improve preclinical selection of promising therapies from the discovery pipeline.
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