Treatment of animal model of ALS with anti GM-CSF antibody

抗GM-CSF抗体治疗ALS动物模型

• 批准号: 23591244
• 负责人: OKUNO Tatsusada
• 金额: $ 3.24万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591244/
• 关键词: ＡＬＳ; GM-CSF; M1/M2; ミクログリア; 炎症; ＪＡＫ２阻害剤; Ｍ１/Ｍ２; Ｍ１／Ｍ２; ALS; セマフォリン

To inhibit GM-CSF-mediated M1 activation in ALS model mice (G93A mSOD1 mice), we used JAK2 inhibitor(R723). Orally adminstered JAK2 inhibitor significantly reduced the number of inflammatory monocytes, as well as the expression level of IFN-gamma and iNOS in the spinal cord tissue of ALS model mice. However, disease progression and survival of mSOD1G93A were not altered by administration of R723.The expression levels of Il-1, Il-6, tumor necrosis factor (TNF), and NADPH oxidase 2 (NOX2) were not altered by R723 treatment.Furthermore, R723 suppressed the expression of Retnla, a marker of neuroprotective M2 microglia.In conclusion,oral administration of JAK2 inhibitor was not effective against ALS symptoms in mSOD1G93A mice, although it suppressed production of several inflammatory molecules. Coincidental suppression of M2 microglia and failure to inhibit critical inflammatory molecules might have contributed to this result.

在ALS模型小鼠(G93A mSOD1小鼠)中，我们使用JAK2抑制剂(R723)来抑制GM-CSF介导的M1激活。口服JAK2抑制剂可显著降低ALS模型小鼠脊髓组织中炎性单核细胞数量，降低脊髓组织中干扰素-γ和诱导型一氧化氮合酶的表达水平。然而，R723不改变mSOD1G93A的疾病进展和存活。R723不改变IL-1、IL-6、肿瘤坏死因子(TNF)和NADPH氧化酶2(NOX2)的表达水平。此外，R723还抑制神经保护性M2的标志物Retnla的表达。结论：口服JAK2抑制剂虽然抑制了几种炎症分子的产生，但对mSOD1G93A小鼠的ALS症状没有疗效。M2小胶质细胞的巧合抑制和未能抑制关键的炎症分子可能是导致这一结果的原因。

项目成果

本研究も含め大阪大学神経内科の神経免疫グループの業績を公開

发表包括本研究在内的大阪大学神经内科神经免疫学组的成果

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• 发表时间: 2013
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• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
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