在慢性期间短期接触托法西提尼布后疾病的改变
bioRxiv : the preprint server for biology
|September 4, 2023
概括
一项新的研究表明,用托法西提尼布准JAK/STAT3通路可以改变. 这种治疗可以长期抑制发作,并扭转模型中的认知缺陷.
科学领域:
- 神经学 神经学
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
背景情况:
- 影响超过5000万人,目前的治疗只能控制症状,在三分之一的患者中失败.
- 现有的治疗方法没有提供疾病修饰以永久消除发作或逆转认知缺陷.
- JAK/STAT通路与有关,显示了最初的快速诱导和随后的激活复苏.
研究的目的:
- 为了确定的疾病修饰的目标.
- 研究JAK/STAT通路在进展中的作用.
- 评估托法西替尼 (CP690550) 在修改的疗效.
主要方法:
- 网络方法应用于动物模型和人类叶切除样本.
- 转录组分析被用来识别疾病修饰标.
- 在的不同阶段分析了JAK/STAT通路的激活模式.
- 评估了托法西替尼对抗发作抑制,认知缺陷和组织病理学的影响.
主要成果:
- 针对最初的JAK/STAT通路激活并没有预防.
- 用托法西提尼布短暂抑制第二波JAK/STAT3激活,持续抑制发作.
- 托法西替尼 (tofacitinib) 挽救了空间记忆缺陷,并缓解了相关的组织病理变化.
- 在最后一剂托法西提尼布后,抑制持续至少2个月.
结论:
- 慢性中炎症性JAK/STAT3信号的重新点燃为疾病修饰提供了治疗窗口.
- 托法西提尼布是FDA批准的药物,显示出作为的疾病修饰治疗的潜力.
- 这项研究强调了一种强大的转录基因方法,用于识别神经系统疾病中的疾病修饰标.
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