PNAS:如何无创监测Duchenne肌营养不良症疾病进展

2018-07-11 海北 MedSci原创

在最近的一项研究中,来自斯坦福大学医学院的研究人员描述了一种在DMD的mdx模型中无创评估疾病进展的新方法。

Duchenne肌营养不良症(DMD)是一种罕见的肌肉退行性疾病,是由于缺乏肌营养不良蛋白造成的。DMD的特征在于肌纤维的进行性丧失,肌肉无力,并最终丧失行走能力和过早死亡。目前没有治愈DMD的方法,改进的疾病监测方法对于新疗法的开发至关重要。

在最近的一项研究中,来自斯坦福大学医学院的研究人员描述了一种在DMD的mdx模型中无创评估疾病进展的新方法。研究人员将该报告小鼠称为营养不良的退行性报告小鼠,其含有在成熟肌纤维中有活性的诱导型CRE反应性荧光素酶报告基因。在这些小鼠中,肌肉变性反映在荧光素酶表达水平的变化中,这可以使用非侵入性生物发光成像来监测。

研究人员监测了这些营养不良报告小鼠的自然史和疾病进展,发现荧光素酶信号的降低与肌肉退化直接相关。研究人员进一步证明该报告小鼠,以及先前报道的再生报告小鼠,成功地揭示了全身施用编码微抗肌萎缩蛋白的重组腺相关病毒-6(rAAV-6)后的有效性。

因此,这些数据证明了这些非侵入性成像模式在监测肌营养不良小鼠模型的疾病进展和治疗反应方面的价值。


原始出处:

Filareto A et al. Monitoring disease activity noninvasively in the mdx model of Duchenne muscular dystrophy. PNAS, 2018; DOI: 10.1073/pnas.1802425115. 


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createdTime=Wed Jul 11 21:47:42 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330896, encodeId=8ae4330896f2, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, 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 11 21:32:07 CST 2018, time=2018-07-11, status=1, ipAttribution=)]
    2018-07-15 docwu2019
  5. 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createdTime=Wed Jul 11 21:47:42 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330896, encodeId=8ae4330896f2, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, 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 11 21:32:07 CST 2018, time=2018-07-11, status=1, ipAttribution=)]
    2019-02-05 makuansheng
  6. 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  7. 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createdTime=Wed Jul 11 21:47:42 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330896, encodeId=8ae4330896f2, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, 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 11 21:32:07 CST 2018, time=2018-07-11, status=1, ipAttribution=)]
  8. 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createdName=yilong5287542, createdTime=Wed May 08 11:46:00 CST 2019, time=2019-05-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330914, encodeId=345e33091487, content=学习一下谢谢.学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zSn0GqHrsfLGSUSR8zwnWWLT4FMl5XH8S58HuZslVkLsAPbXDXaliagK7TOxQfmngKibG1yrDonepCLDkcxGk8hS/0, createdBy=b8282062892, createdName=changjiu, createdTime=Wed Jul 11 22:18:30 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330906, encodeId=b2ab3309061f, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Wed Jul 11 21:47:42 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330896, encodeId=8ae4330896f2, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, 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 11 21:32:07 CST 2018, time=2018-07-11, status=1, ipAttribution=)]
    2018-07-11 changjiu

    学习一下谢谢.学习一下

    0

  9. 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createdTime=Wed Jul 11 21:47:42 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330896, encodeId=8ae4330896f2, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, 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 11 21:32:07 CST 2018, time=2018-07-11, status=1, ipAttribution=)]
    2018-07-11 医者仁心5538

    学习了

    0

  10. 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createdTime=Wed Jul 11 21:47:42 CST 2018, time=2018-07-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=330896, encodeId=8ae4330896f2, content=了解一下.谢谢分享!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, 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 11 21:32:07 CST 2018, time=2018-07-11, status=1, ipAttribution=)]
    2018-07-11 天地飞扬

    了解一下.谢谢分享!

    0

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研究发现,大部分杜氏肌营养不良症患者接受Ataluren治疗后症状无显著改善,但对于基线6MWD测试成绩300-400m之间的患者,治疗显示出显著的效果。基于6MWD的患者分层是预测患者治疗受益的有效途径,未来的研究将集中于患者的个性化治疗开展

Nat Commun:减少肌脂蛋白的表达或可用于杜氏肌营养不良的治疗

肌脂蛋白(SLN)是肌肉/内质网(SR)Ca 2+ ATP酶(SERCA)的抑制剂,在杜氏肌营养不良(DMD)患者和动物模型中肌肉里表达异常升高。本研究中,研究人员发现减少SLN的水平可改善重症肌营养不良蛋白/肌萎缩蛋白双重突变体(mdx:utr - / -)DMD模型小鼠的营养不良。SLN基因的一个等位基因的种系失活可使SLN的表达正常化,恢复SERCA的功能,减轻骨骼肌和心脏病理,改善肌肉再生

Lancet:长期糖皮质激素疗法对杜氏肌营养不良患者疾病里程碑和死亡率的影响

研究认为长期的糖皮质激素治疗方案可降低杜氏肌营养患者的疾病进展风险,延长患者生存期

Science Advances:重磅!研究人员使用CRISPR-Cpf1治疗杜氏肌营养不良

异常心肌细胞(左)和修复之后的心肌细胞(右)2017年4月18日讯 /生物谷BIOON /——德州大学西南医学研究中心研究员利用新的基因编辑酶CRISPR-Cpf1在实验室了人类细胞和老鼠体内的杜氏肌营养不良。 该研究组过去使用原有的基因编辑系统CRISPR-Cas9纠正患有此病的老鼠模型和人类细胞内的杜氏肌缺陷。在目前的研究中,他们使用一种新的基因编辑系统,用于修复老鼠模型和人类细胞中

Ann Neurol:超声定量检测用于杜氏肌营养不良患儿的诊断

超声显像的灰度级(GSL)以及回波信号测量的定量背散射分析(QBA)均表现出检测杜氏肌营养不良肌肉功能异常的敏感性,未来研究将针对超声检查用于治疗效果的评价开展

Neurology:Eteplirsen治疗杜氏肌营养不良长期疗效研究

研究证实,Eteplirsen长期治疗可诱导肌细胞穿透、外显子跳跃并促进新的肌萎缩蛋白表达