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NEJM:一个持久的PCSK9干扰RNAi治疗抑制剂-Inclisiran

2016-11-14 xing.T MedSci原创

在这项1期试验中,运用Inclisiran没有观察到严重的不良反应。300mg或更大剂量(单次或多次剂量)能显著降低LDL胆固醇和PCSK9水平至少6个月。

近日,顶级医学期刊NEJM上发表了一篇研究文章,旨在介绍了Inclisiran,一种长效的干扰RNA治疗抑制剂,能够抑制枯草溶菌素转化酶9(PCSK9)的合成,PCSK9可靶向降低低密度脂蛋白(LDL)胆固醇水平。
 
在1期试验中,研究人员将LDL胆固醇水平超过100mg/dL的健康志愿者按3:1的比例随机分组,分别接受皮下注射Inclisiran或安慰剂,Inclisiran组的参与者单次给予递增剂量(剂量为25、100、300、500或800 mg)或多次给药(125 mg,每周四次;250mg,每隔一周两次;300或500 mg每月两次,有无合用他汀类药物治疗);各剂量组有4-8名参与者,研究者对其安全性、副作用和药效学指标(PCSK9水平、LDL胆固醇水平以及探测性脂质变量)进行评估。
 
研究者发现Inclisiran最常见的不良反应为咳嗽、骨骼肌肉疼痛、鼻咽炎、头痛、后背痛、腹泻等,所有不良反应均为轻度或中度,没有严重的不良反应或因不良反应而停药。有一名参与者出现γ-谷氨酰转移酶3级升高,研究者认为这与他汀类药物治疗相关。在单剂量阶段,Inclisiran剂量超过300mg就可以引起PCSK9水平降低(最小二乘平均值从基线到84天减少了74.5%),以及剂量超过100mg就可降低LDL胆固醇水平(最小二乘平均值从基线减少了50.6%)。在给予超过300mg剂量在180天,仍然可以减少PCSK9和LDL胆固醇水平。所有多剂量方案都能降低PCSK9(最小二乘平均值从基线到84天减少了83.8%)和LDL胆固醇(最小二乘平均值从基线到84天减少了59.7%)水平。
 
在这项1期试验中,运用Inclisiran没有观察到严重的不良反应。300mg或更大剂量(单次或多次剂量)能显著降低LDL胆固醇和PCSK9水平至少6个月。
 
原始出处:

 
Kevin Fitzgerald, et al. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. NEJM. November 13, 2016.DOI:10.1056/NEJMoa1609243.

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    2017-07-22 FukaiBao
  2. [GetPortalCommentsPageByObjectIdResponse(id=1777242, encodeId=16a91e77242b0, content=<a href='/topic/show?id=678d5348a6' target=_blank style='color:#2F92EE;'>#Csk#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5348, encryptionId=678d5348a6, topicName=Csk)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=979839152460, createdName=FukaiBao, createdTime=Sat Jul 22 22:35:00 CST 2017, time=2017-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851369, encodeId=c6ba185136980, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed May 17 07:35:00 CST 2017, time=2017-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685583, encodeId=645e1685583fa, content=<a href='/topic/show?id=a340138e48a' target=_blank style='color:#2F92EE;'>#PCS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13874, encryptionId=a340138e48a, topicName=PCS)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=173d28230918, createdName=Tamikia, createdTime=Sat Dec 17 17:35:00 CST 2016, time=2016-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=166109, encodeId=00b81661090d, content=期待更进一步的激动人心的结果,来证明RNAi成为药物的巨大前景。, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74411664721, createdName=geneandu, createdTime=Tue Dec 27 15:43:36 CST 2016, time=2016-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1751656, encodeId=e2601e51656d0, content=<a href='/topic/show?id=2c2c1553e56' target=_blank style='color:#2F92EE;'>#RNAi#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15537, encryptionId=2c2c1553e56, topicName=RNAi)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d9d436366397, createdName=yinxm8315, createdTime=Sat Mar 04 11:35:00 CST 2017, time=2017-03-04, status=1, ipAttribution=)]
    2017-05-17 jklm09
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    2016-12-17 Tamikia
  4. [GetPortalCommentsPageByObjectIdResponse(id=1777242, encodeId=16a91e77242b0, content=<a href='/topic/show?id=678d5348a6' target=_blank style='color:#2F92EE;'>#Csk#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5348, encryptionId=678d5348a6, topicName=Csk)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=979839152460, createdName=FukaiBao, createdTime=Sat Jul 22 22:35:00 CST 2017, time=2017-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851369, encodeId=c6ba185136980, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed May 17 07:35:00 CST 2017, time=2017-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1685583, encodeId=645e1685583fa, content=<a href='/topic/show?id=a340138e48a' target=_blank style='color:#2F92EE;'>#PCS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13874, encryptionId=a340138e48a, topicName=PCS)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=173d28230918, createdName=Tamikia, createdTime=Sat Dec 17 17:35:00 CST 2016, time=2016-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=166109, encodeId=00b81661090d, content=期待更进一步的激动人心的结果,来证明RNAi成为药物的巨大前景。, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=74411664721, createdName=geneandu, createdTime=Tue Dec 27 15:43:36 CST 2016, time=2016-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1751656, encodeId=e2601e51656d0, content=<a href='/topic/show?id=2c2c1553e56' target=_blank style='color:#2F92EE;'>#RNAi#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15537, encryptionId=2c2c1553e56, topicName=RNAi)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d9d436366397, createdName=yinxm8315, createdTime=Sat Mar 04 11:35:00 CST 2017, time=2017-03-04, status=1, ipAttribution=)]
    2016-12-27 geneandu

    期待更进一步的激动人心的结果,来证明RNAi成为药物的巨大前景。

    0

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    2017-03-04 yinxm8315
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