Nat Med：重磅新药可对抗帕金森！“生命的颤抖”或有望终结！

2018-07-04 Ruthy,Zoe 转化医学网

帕金森病（PD）是一种常见的神经系统变性疾病，具有高度异质性。不同病人疾病进展的速度不同，目前尚不能治愈。近期，约翰斯·霍普金斯大学的科学家们开发出了一种实验性药物，可缓解帕金森病的症状并延缓其进展！这意味着患者有望终结这种“生命的颤抖”，摆脱帕金森的噩梦！

导读

帕金森病（PD）是一种常见的神经系统变性疾病，具有高度异质性。不同病人疾病进展的速度不同，目前尚不能治愈。近期，约翰斯·霍普金斯大学的科学家们开发出了一种实验性药物，可缓解帕金森病的症状并延缓其进展！这意味着患者有望终结这种“生命的颤抖”，摆脱帕金森的噩梦！

研究人员表示，这种药物名为NLY01，与部分糖尿病药物的结构相似，在人脑细胞和活小鼠模型的实验中，该药物有效阻断了脑细胞的降解，从而缓解了帕金森病的症状。他们指出该药预计将于今年进入临床试验阶段。研究结果以《Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease》为题发表。

“NLY01对目标神经细胞具有惊人的保护作用，”约翰霍普金斯大学医学院细胞工程研究所主任的Ted Dawson博士解释到，如果NLY01在人类临床试验中获得成功，将是帕金森病患者莫大的福音，因为它针对的将不仅仅是肌肉僵硬、痉挛运动、疲劳、头晕、痴呆等症状，还可以直接阻断帕金森病的进展。

根据研究人员的说法，NLY01可与细胞表面的胰高血糖素样肽-1受体结合，这个过程和与其结构相似的糖尿病药物对2型糖尿病的作用相似。为了证实NLY01的疗效，Dawson团队在人源性星形胶质细胞，小胶质细胞和神经元上测试了NLY01。他们发现小胶质细胞的NLY01的结合位点比其他细胞类型高2倍，而且帕金森病患者NLY01结合位点的使用率是普通人的10倍。

NLY01阻断侵袭性活化星形胶质细胞成熟

我们知道，小胶质细胞分泌的化学信号可促进星形胶质细胞的成熟，而在帕金森患者大脑中，成熟的是极具侵袭性的活化星形胶质细胞，这种细胞可吞噬大脑神经元间的连接，导致神经元死亡。研究人员指出NLY01可能是通过阻断该过程来对抗帕金森病。

NLY01诱导帕金森小胶质细胞激活信号关闭

在人脑神经元的实验室初步实验中，Dawson团队用NLY01处理了人类帕金森小胶质细胞，发现这些小胶质细胞的激活信号关闭。当这些细胞与健康星形胶质细胞结合时，健康细胞并不会转化为侵袭性活化星形胶质细胞，始终保持健康状态。而且NLY01处理后的细胞还可抑制侵袭性活化星形胶质细胞的活动，为健康神经元构筑了一个防护层，使其不受疾病状态细胞的影响。

NLY01抑制侵袭性活化星形胶质细胞活动

随后，Dawson团队进入了动物实验，他们用NLY01治疗了帕金森小鼠。结果显示用NLY01治疗的帕金森小鼠可维持正常的身体功能，并且没有发现多巴胺神经元的损失，这表明该药物可以预防帕金森病的发展，而且，用NLY01治疗的小鼠大脑中几乎没有出现帕金森病神经退行性病变的迹象。更令人惊讶的结果是，NLY01治疗还延长了20只遗传性帕金森病小鼠超过120天的寿命。

NLY01延长遗传性帕金森病小鼠寿命

但是，Dawson博士警告说，NLY01目前仍属于实验药物，必须进行必要的安全性和有效性测试。但根据其他类似药物的安全性，其在人类帕金森病的治疗中应该可以有令人满意的结果。

原始出处：Seung Pil Yun, Tae-In Kam, Nikhil Panicker, et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease. Nature Medicine (2018)

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2018-08-26 123aa375m26暂无昵称

心急的等待着，希望家人能赶上药的上市啊。祈祷。

61 0
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2019-04-17 liye789132251

#Nat#

26 0
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2018-07-06 xxxx1054

#重磅#

32 0
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2018-07-06 ms3994565386320060

#Med#

39 0
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2018-07-06 张新亮1853311252142e2fm

好文献学习了

62 0
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2018-07-05 坚强007

向科学家致敬!!致敬!!!

55 0
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2018-07-05 易水河

不容易的呀!

55 0
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2018-07-04 戒馋，懒，贪

谢谢分享学习了

61 0
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2018-07-04 医者仁心5538

学习了

23 0
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2018-07-04 天地飞扬

了解一下.谢谢分享!

24 0

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