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SCI TRANSL MED:ALS的新药效学标志物

2017-03-30 xing.T MedSci原创

这些结果表明,跟踪CSF多(GP)蛋白为评估针对G4C2 RNA扩增的疗法提供了一种手段,在有症状的C9ORF72重复扩增的载带着和那些有望受益于早期干预治疗的无症状患者。

肌萎缩性脊髓侧索硬化症(ALS)是一种破坏性运动神经元疾病目前还没有有效的治疗方案。然而,C9ORF72基因G4C2序列重复扩增的发现是ALS最常见的遗传原因,为这种类型的ALS治疗干预开辟了新途径。

G4C2序列重复扩增的RNAs和这些转录本合成的重复多肽蛋白被认为在C9ORF72相关的ALS中发挥关键作用(c9ALS)。针对G4C2 RNA的治疗,如反义寡核苷酸(ASO)和小分子,因此正在被积极研究之中。在这样的治疗从基础到临床的局限主要是在临床试验使用过程中缺乏药效学标志物。

近日,Science Translational Medicine杂志发表了一篇研究文章,研究人员探讨了从G4C2 RNA转录而来的多(GP)蛋白能否实现这样一个目的。多(GP)蛋白在c9ALS的脑脊液(CSF)和外周血单个核细胞中均可以被检测到,值得注意的是,无症状的C9ORF72突变携带者也可以检测到。此外,CSF多(GP)蛋白随着时间的推移保持相对不变,有望用于测量对潜在治疗方法的生化反应。研究人员采用针对G4C2 RNA的ASOS治疗c9ALS病人细胞或c9ALS小鼠模型可以降低胞内和胞外多(GP)蛋白。这种减少伴随着G4C2 RNA和G4C2 RNA介导的下游事件减少。

这些结果表明,跟踪CSF多(GP)蛋白为评估针对G4C2 RNA扩增的疗法提供了一种手段,在有症状的C9ORF72重复扩增的载带着和那些有望受益于早期干预治疗的无症状患者。

原始出处:

Tania F. Gendron,et al. Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72-associated amyotrophic lateral sclerosis.Science Translational Medicine . http://stm.sciencemag.org/content/9/383/eaai7866

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    2017-11-29 bsmagic9140
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    2017-07-02 lsndxfj
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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=183787, encodeId=fd95183e8748, content=好。。。。。, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuLkkiaEa1J4A8RpxoFZ1V1SxXfAZoXeffWFsO8s5qTklzZa8iasdibic8OcUkdCpTyFeWuy5KePlj8Sm/0, createdBy=c4372036703, createdName=liur63, createdTime=Thu Mar 30 12:54:28 CST 2017, time=2017-03-30, status=1, ipAttribution=)]
    2017-03-31 jin321

    何时能有突破天际

    0

  8. 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target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, 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=Sat Apr 01 03:48:00 CST 2017, time=2017-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=184030, encodeId=687318403078, content=何时能有突破天际, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xjZ9qh3bhXrJtUlmycKGfQKPuADVZQsdNAQj5IrHHlzbGsDwScictBgogYRk8KhicpgEKwTEfOHgqw/0, createdBy=bc931611963, createdName=jin321, createdTime=Fri Mar 31 14:37:55 CST 2017, time=2017-03-31, status=1, ipAttribution=), 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=183787, encodeId=fd95183e8748, content=好。。。。。, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuLkkiaEa1J4A8RpxoFZ1V1SxXfAZoXeffWFsO8s5qTklzZa8iasdibic8OcUkdCpTyFeWuy5KePlj8Sm/0, createdBy=c4372036703, createdName=liur63, createdTime=Thu Mar 30 12:54:28 CST 2017, time=2017-03-30, status=1, ipAttribution=)]
    2017-03-30 天涯183

    非常好的研究

    0

  9. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=183787, encodeId=fd95183e8748, content=好。。。。。, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuLkkiaEa1J4A8RpxoFZ1V1SxXfAZoXeffWFsO8s5qTklzZa8iasdibic8OcUkdCpTyFeWuy5KePlj8Sm/0, createdBy=c4372036703, createdName=liur63, createdTime=Thu Mar 30 12:54:28 CST 2017, time=2017-03-30, status=1, ipAttribution=)]
    2017-03-30 Chongyang Zhang

    签到学习了很多。

    0

  10. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=183787, encodeId=fd95183e8748, content=好。。。。。, beContent=null, objectType=article, channel=null, level=null, likeNumber=112, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuLkkiaEa1J4A8RpxoFZ1V1SxXfAZoXeffWFsO8s5qTklzZa8iasdibic8OcUkdCpTyFeWuy5KePlj8Sm/0, createdBy=c4372036703, createdName=liur63, createdTime=Thu Mar 30 12:54:28 CST 2017, time=2017-03-30, status=1, ipAttribution=)]
    2017-03-30 liur63

    好。。。。。

    0

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“咱当兵的人,有啥不一样”…研究证明,当兵的人还真的有不一样的地方。目前关于服兵役的人群的研究逐渐增多,关于服兵役与肌萎缩性脊髓侧索硬化症(ALS)的研究,只有志愿者参与的前瞻性队列研究,认为服兵役会导致肌萎缩性脊髓侧索硬化症(ALS)的风险增加。为了验证以及更准确的研究该问题,Weisskopf MG等人以人群为基础,进行了一项队列研究。该研究的纳入人群来自美国的一项基于代表人群的纵向死亡率的研

Science:研究发现免疫细胞在ALS中发挥意想不到的作用

在最新发表于《Science》期刊的研究中,Cedars-Sinai医学中心研究科学家们发现,大脑中的免疫细胞在肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)的发展中发挥直接作用,为针对这种神经退行性疾病的新疗法提供了希望。 研究人员专注于被称为C9orf72的基因,该基因中的突变会导致ALS和额颞叶痴呆(FTD)。FTD是另一种神经系统疾病,通常会造成患者

Science:科学家发现ALS和FTD等神经退行性疾病病因

来自美国梅奥诊所(Mayo Clinic)的科学家们构建出了一种新型小鼠,其显示出与肌萎缩侧索硬化症(ALS,又称渐冻人症)和额颞痴呆(FTD)最常见的遗传形式相关的一些症状和神经退行性变。ALS和FTD这两种疾病都是由于C9ORF72基因突变引起。这项研究发布在近期的《科学》(Science)杂志上。  美国有3万多ALS患者,ALS破坏了控制包括说话、行走、呼吸和吞咽等基本动作的神

真正的读心术来了,将想法变成文字不再只是想象!

去年火爆的冰桶挑战将ALS带入大家的视线,冰水浇头的那一刻也让很多人体会到了渐冻人无法说话和运动的痛苦。作为ALS的代表人物,史蒂夫·霍金有一款神奇的椅子,通过眼球运动选取屏幕上的文字再由合音播放器来发声。现在,除了这种大脑-声音的转换模式,大脑-文本的转换系统也将实现,可以将大脑活动转换成文字!最近发表在Frontiersin Neuroscience上的文章进行了一项实验:让7名患者大声朗读林

Nature:常见基因突变为何会引发痴呆

近日,一项刊登在国际杂志Nature上的研究论文中,来自约翰霍普金斯大学的研究人员通过研究揭示常见的基因突变如何引发大脑损伤相关的肌萎缩侧索硬化症(ALS)和额颞痴呆(frontotemporal dementia,FTD),研究者表示,位于人类9号染色体上的C9orf72基因的改变会促进RNA分子阻断蛋白运输的关键通路,从而引发大脑细胞核外部的分子“交通拥挤”,进而影响大脑的正常功能。研究者Je

Nature Medicine:运动神经元丢失MHCI导致ALS星形胶质细胞毒性

肌萎缩侧索硬化(Amyotrophic lateral sclerosis,ALS)也被称为卢伽雷氏症,是一种毁灭性的神经退行性疾病,会导致控制肌肉的运动神经元进行性死亡。最终,ALS患者将失去行走、活动、吞咽和呼吸能力。 直到最近,星形胶质细胞在运动神经元死亡中所扮演的角色一直是个谜。在最新发表于《Nature Medicine》的研究中,美国全国儿童医院(Nationwide Childre

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