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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。

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    2019-04-17 liye789132251
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    2018-07-06 xxxx1054
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    2018-07-06 张新亮1853311252142e2fm

    好文献学习了

    0

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    2018-07-05 坚强007

    向科学家致敬!!致敬!!!

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=340985, encodeId=3b9134098535, content=心急的等待着,希望家人能赶上药的上市啊。祈祷。, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0142426904, createdName=123aa375m26暂无昵称, createdTime=Sun Aug 26 22:12:22 CST 2018, time=2018-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883154, encodeId=9b7b1883154d4, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Apr 17 06:17:00 CST 2019, time=2019-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549345, encodeId=4b921549345b9, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Jul 06 12:17:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608940, encodeId=25dd160894021, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Fri Jul 06 12:17:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329640, encodeId=d9a6329640df, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Fri Jul 06 06:19:04 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329496, encodeId=379d32949617, content=向科学家致敬!!致敬!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e5171668917, createdName=坚强007, createdTime=Thu Jul 05 12:12:43 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329493, encodeId=cb6132949373, content=不容易的呀!, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKibA62IFMeUJEmSyIe8DvYFeERuOsfrRd8iano7nENqQU1dRR3tqeQOUL3eqgYgEZRT2t2iaEsib0JEw/132, createdBy=66771693911, createdName=易水河, createdTime=Thu Jul 05 11:47:56 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329336, encodeId=f70a32933674, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Wed Jul 04 22:55:44 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329330, encodeId=4bdb32933054, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Wed Jul 04 22:27:07 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329325, encodeId=2dea3293256b, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Wed Jul 04 22:02:22 CST 2018, time=2018-07-04, status=1, ipAttribution=)]
    2018-07-05 易水河

    不容易的呀!

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=340985, encodeId=3b9134098535, content=心急的等待着,希望家人能赶上药的上市啊。祈祷。, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0142426904, createdName=123aa375m26暂无昵称, createdTime=Sun Aug 26 22:12:22 CST 2018, time=2018-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883154, encodeId=9b7b1883154d4, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Apr 17 06:17:00 CST 2019, time=2019-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549345, encodeId=4b921549345b9, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Jul 06 12:17:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608940, encodeId=25dd160894021, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Fri Jul 06 12:17:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329640, encodeId=d9a6329640df, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Fri Jul 06 06:19:04 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329496, encodeId=379d32949617, content=向科学家致敬!!致敬!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e5171668917, createdName=坚强007, createdTime=Thu Jul 05 12:12:43 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329493, encodeId=cb6132949373, content=不容易的呀!, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKibA62IFMeUJEmSyIe8DvYFeERuOsfrRd8iano7nENqQU1dRR3tqeQOUL3eqgYgEZRT2t2iaEsib0JEw/132, createdBy=66771693911, createdName=易水河, createdTime=Thu Jul 05 11:47:56 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329336, encodeId=f70a32933674, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Wed Jul 04 22:55:44 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329330, encodeId=4bdb32933054, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Wed Jul 04 22:27:07 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329325, encodeId=2dea3293256b, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Wed Jul 04 22:02:22 CST 2018, time=2018-07-04, status=1, ipAttribution=)]
    2018-07-04 戒馋,懒,贪

    谢谢分享学习了

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=340985, encodeId=3b9134098535, content=心急的等待着,希望家人能赶上药的上市啊。祈祷。, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0142426904, createdName=123aa375m26暂无昵称, createdTime=Sun Aug 26 22:12:22 CST 2018, time=2018-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1883154, encodeId=9b7b1883154d4, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Wed Apr 17 06:17:00 CST 2019, time=2019-04-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1549345, encodeId=4b921549345b9, content=<a href='/topic/show?id=f7879600061' target=_blank style='color:#2F92EE;'>#重磅#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=96000, encryptionId=f7879600061, topicName=重磅)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3acc14121561, createdName=xxxx1054, createdTime=Fri Jul 06 12:17:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1608940, encodeId=25dd160894021, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Fri Jul 06 12:17:00 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329640, encodeId=d9a6329640df, content=好文献学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b5a62240667, createdName=张新亮1853311252142e2fm, createdTime=Fri Jul 06 06:19:04 CST 2018, time=2018-07-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329496, encodeId=379d32949617, content=向科学家致敬!!致敬!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e5171668917, createdName=坚强007, createdTime=Thu Jul 05 12:12:43 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329493, encodeId=cb6132949373, content=不容易的呀!, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKibA62IFMeUJEmSyIe8DvYFeERuOsfrRd8iano7nENqQU1dRR3tqeQOUL3eqgYgEZRT2t2iaEsib0JEw/132, createdBy=66771693911, createdName=易水河, createdTime=Thu Jul 05 11:47:56 CST 2018, time=2018-07-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329336, encodeId=f70a32933674, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=123, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Wed Jul 04 22:55:44 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329330, encodeId=4bdb32933054, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Wed Jul 04 22:27:07 CST 2018, time=2018-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=329325, encodeId=2dea3293256b, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2019/12/23/2f51002e1349ccda5be11c1eea1e1e60.jpg, createdBy=a22097948, createdName=天地飞扬, createdTime=Wed Jul 04 22:02:22 CST 2018, time=2018-07-04, status=1, ipAttribution=)]
    2018-07-04 医者仁心5538

    学习了

    0

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    2018-07-04 天地飞扬

    了解一下.谢谢分享!

    0

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导 读 颤颤巍巍的老人于我们的生活中随处可见,他们可能罹患了帕金森氏症。除了手抖之外,帕金森患者同时还伴有肌肉僵硬,动作迟缓等症状,无法彻底治愈是他们内心的隐痛。有关数据统计,德国约有22万人受到帕金森病的影响,而我国65岁以上人群患病率大约是1.7%,数值着实令人心惊!

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研究认为,早期深部脑电刺激联合适当的药物治疗可有效患者帕金森患者静息震颤症状,其效果优于单纯的药物治疗

Lancet Neurol:特发性快速眼动睡眠行为障碍患者神经病理学研究

研究发现,特发性快速眼动睡眠行为障碍患者其周围神经及蓝斑的病理与帕金森确诊患者极为相似,患者表现为去甲肾上腺素能丘脑失神经,但大部分患者壳核多巴胺能储存能力正常。该研究结果证实了α-突触核蛋白聚集在帕金森早期病理进展过程中发挥的关键作用

Lundbeck制药的帕金森新疗法

H. Lundbeck A / S(Lundbeck)再次扩大了其临床开发项目的管线,并启动了一项关于帕金森病潜在新疗法的I期研究。该化合物为Lu AF28996,由Lundbeck发明,现在将作为其临床开发的第一部分在健康志愿者中进行研究。

Stem Cell Rep:动物所利用胚胎干细胞分化的神经细胞改善帕金森猴运动障碍

近日,中国科学院动物研究所干细胞与再生医学创新研究院胡宝洋课题组与周琪课题组合作在Stem Cell Reports杂志在线发表了题为Human Clinical-grade Parthenogenetic ESC-derived Dopaminergic Neurons Recover Locomotive Defects of Nonhuman Primate Models of Parkin

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