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Science Translational Medicine:1克就能毒死百万人,世界强大毒药肉毒素,有解药了!

2021-01-08 生物世界 Bio生物世界

肉毒杆菌毒素,简称肉毒素,是由致命的肉毒杆菌在繁殖过程中所产生的一种神经毒素蛋白,是迄今为止发现的毒性最强的生物毒素,肉毒素对人类的致死剂量是1钠克/千克体重。

肉毒杆菌毒素,简称肉毒素,是由致命的肉毒杆菌在繁殖过程中所产生的一种神经毒素蛋白,是迄今为止发现的毒性最强的生物毒素,肉毒素对人类的致死剂量是1钠克/千克体重,也就是说,1克肉毒素能够毒死200万个50公斤体重的人。

由于肉毒素能使肌肉暂时麻痹,医学界原先将肉毒素用于治疗面部痉挛和其他肌肉运动紊乱症。治疗过程中发现,肉毒素在消除皱纹方面有着异乎寻常的功能,因此,现在注射肉毒素除皱的微整形风靡全球。

肉毒素会在保存不当的食物、受感染的伤口中生在的细菌中出现,但肉毒素中毒很少见,每年记录在案的不到200例。但随着肉毒素整容的风靡,也可能会出现操作失误导致中毒,而且,由于肉毒素极其强大的毒性,因此还可被用作生化武器。

目前的治疗治疗肉毒素中毒的方法是抗体鸡尾酒疗法,该疗法可以使血液中的毒素失活,但这些抗体不能进入神经,当中毒症状出现时,一些毒素已经进入神经,抗体已经无法触及,中毒者会出现持续性神经阻滞和肌肉麻痹,必须依赖重症监护和呼吸机才能生存,治疗费用非常昂贵,一旦出现大规模爆发,将会使医疗系统崩溃。

2021年1月6日,Science 子刊 Science Translational Medicine 同期发表了两篇来自不同团队的研究肉毒素解药的论文。两个研究团队各自开发了类似的方法,将能够中和肉毒素的抗体与改造修饰后的肉毒素组成融合蛋白,这种融合蛋白能够更好地进入神经,从而清除之前无法触及的神经内的肉毒素。

使用这种方法,研究团队成功拯救了肉毒素中毒的小鼠、豚鼠以及猴子,这种方法如果在人体同样有效的话,将会是第一个逆转细胞内毒素麻痹作用的药物,从而使中毒者不再需要呼吸机生存。

来自纽约大学和波士顿儿童医院的两个研究团队,使用了一种巧妙的方法,能够让中和肉毒素的抗体成功进入神经细胞。研究团队对肉毒素进行了改造修饰,改造后的肉毒素不再具有致死毒性,而且能够更好地进入神经细胞。

然后研究团队将来自羊驼的纳米抗体与修饰过的肉毒素结合,这种改造修饰的肉毒素,就像是“特洛伊木马”。将治疗用的纳米抗体带入神经,然后纳米抗体快速中和肉毒素。

两个研究团队分别在小鼠、豚鼠、猴子上测试了这种方法的治疗效果,治疗效果明显。其中,6只肉毒素中毒的猴子,在接受该方法治疗后成功存活,而7只未接受治疗的猴子都没能活过3.5天。

据悉,这两个研究团队都在寻求美国食品药品监督管理局(FDA)对该疗法的批准,由于在人体测试剧毒毒素解药功效不符合道德标准,可以基于动物实验结果授权该药物,但这必然要经历更加漫长而又艰难的历程,但好在,这两项研究已经是一个很好的开端。

原始出处:

[1]Patrick M. McNutt,Edwin J. Vazquez-Cintron,Luis Tenezaca,et al.Neuronal delivery of antibodies has therapeutic effects in animal models of botulism.Science Translational Medicine  06 Jan 2021:
Vol. 13, Issue 575, eabd7789DOI: 10.1126/scitranslmed.abd7789

[2]Shin-Ichiro Miyashita,Jie Zhang,Sicai Zhang,et al.Delivery of single-domain antibodies into neurons using a chimeric toxin–based platform is therapeutic in mouse models of botulism. Science Translational Medicine  06 Jan 2021:Vol. 13, Issue 575, eaaz4197DOI: 10.1126/scitranslmed.aaz4197

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  4. [GetPortalCommentsPageByObjectIdResponse(id=1657397, encodeId=7cca165e397f4, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Tue Jun 08 12:12:50 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795901, encodeId=c1781e959015c, content=<a href='/topic/show?id=42211e757d7' target=_blank style='color:#2F92EE;'>#Translation#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17757, encryptionId=42211e757d7, topicName=Translation)], attachment=null, authenticateStatus=null, 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  5. 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likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sun Jan 10 06:12:50 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1610847, encodeId=da45161084ebf, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, 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=Sun Jan 10 06:12:50 CST 2021, time=2021-01-10, status=1, ipAttribution=)]
    2021-06-02 jeanqiuqiu
  6. 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    2021-05-08 kalseyzl
  7. 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topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sun Jan 10 06:12:50 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555493, encodeId=40df155549338, content=<a href='/topic/show?id=dbb48086175' target=_blank style='color:#2F92EE;'>#肉毒素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80861, encryptionId=dbb48086175, topicName=肉毒素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2f3a14615017, createdName=tulenzi, createdTime=Sun Jan 10 06:12:50 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577760, encodeId=576715e77603e, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sun Jan 10 06:12:50 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1610847, encodeId=da45161084ebf, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, 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=Sun Jan 10 06:12:50 CST 2021, time=2021-01-10, status=1, ipAttribution=)]
    2021-01-10 jichang
  8. [GetPortalCommentsPageByObjectIdResponse(id=1657397, encodeId=7cca165e397f4, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Tue Jun 08 12:12:50 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795901, encodeId=c1781e959015c, content=<a href='/topic/show?id=42211e757d7' target=_blank style='color:#2F92EE;'>#Translation#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17757, encryptionId=42211e757d7, topicName=Translation)], attachment=null, authenticateStatus=null, 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createdTime=Wed Jun 02 12:12:50 CST 2021, time=2021-06-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1773904, encodeId=fda01e7390405, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a9a038523631, createdName=kalseyzl, createdTime=Sat May 08 20:12:50 CST 2021, time=2021-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376237, encodeId=344413e6237bc, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, 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likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sun Jan 10 06:12:50 CST 2021, time=2021-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1610847, encodeId=da45161084ebf, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, 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=Sun Jan 10 06:12:50 CST 2021, time=2021-01-10, status=1, ipAttribution=)]
    2021-01-10 tulenzi
  9. [GetPortalCommentsPageByObjectIdResponse(id=1657397, encodeId=7cca165e397f4, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Tue Jun 08 12:12:50 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795901, encodeId=c1781e959015c, content=<a href='/topic/show?id=42211e757d7' target=_blank style='color:#2F92EE;'>#Translation#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17757, encryptionId=42211e757d7, topicName=Translation)], attachment=null, authenticateStatus=null, 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  10. 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