J NEUROSCI：新药通过抑制大脑炎症治疗多种神经系统疾病

美国西北大学费因伯格医学院开发的一类新的药物，初步显示出对老年痴呆症，帕金森氏症，多发性硬化症和创伤性脑损伤的治疗效果，这主要是通过减少大脑的炎症实现的。西北大学最近获批了这一类新药的专利，并已授权生物技术公司完成了首次1期临床试验。

该类药物针对一类特定类型的大脑炎症。这种炎症是这些神经系统疾病和脑外伤和中风的一个共同特点。这种大脑的炎症，也被称为神经炎症，被越来越多地认为在这些以渐进性破坏为特征的慢性疾病和脑损伤中发挥重大作用。

相比目前正在进行测试的防止大脑发生斑块的治疗方法，新药物--mw151和mw189--通过缓解大脑炎症，提供了一种完全不同的对老年痴呆症的治疗方法。淀粉样斑块是一个疾病的指标，但不是一个已被证实的病因。

一项发表在神经学杂志（Journal of Neuroscience）的新临床研究报告说，给予老年痴呆症易患小鼠，某种西北大学研发的新药MW01-2-151SRM ，可以防止小鼠老年痴呆的全面发生。本研究，还确定了该药物最佳的治疗时间窗。研究者说，该药物可以口服并容易穿过血脑屏障。西北大学费因伯格医学院分子药理学和生物化学沃特森教授说，"这种药物可能成为预防老年痴呆症发生发展的药物库的一员。"

其他研究同时证实了，该药物对帕金森氏症，多发性硬化症和创伤性脑损伤的治疗效果。

本文编译自New drug could treat Alzheimer's, multiple sclerosis and brain injury

doi:10.1016/j.cell.2011.10.017
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Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction in a Mouse Model That Exhibits Age-Dependent Progression of Alzheimer's Disease-Related Pathology

Adam D. Bachstetter1,Christopher M. Norris1,2,Pradoldej Sompol1,Donna M. Wilcock1,3,Danielle Goulding1,Janna H. Neltner1,4,Daret St. Clair1,5,7,D. Martin Watterson8, andLinda J. Van Eldik1,6

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that selectively attenuates proinflammatory cytokine production at low doses. MW-151 was tested in an APP/PS1 knock-in mouse model that exhibits increases in AD-relevant pathology progression with age, including increases in proinflammatory cytokine levels. Drug was administered during two distinct but overlapping therapeutic time windows of early stage pathology development. MW-151 treatment attenuated the increase in microglial and astrocyte activation and proinflammatory cytokine production in the cortex and yielded improvement in neurologic outcomes, such as protection against synaptic protein loss and synaptic plasticity impairment. The results also demonstrate that the therapeutic time window is an important consideration in efficacy studies of drugs that modulate glia biological responses involved in pathology progression and suggest that such paradigms should be considered in the development of new therapeutic regimens that seek to delay the onset or slow the progression of AD.