SCI TRANS MED:临床数据显示,脑部AAV疗法拯救婴儿致命遗传疾病

2020-12-04 haibei MedSci原创

7名儿童中的4名儿童的灰质体积丢失较慢,运动和语言功能下降率分别降低42.4和47.5%。AAVrh.10hCLN2的脑内给药可延缓CLN2病患儿的疾病进展。

CLN2病,又称晚期婴儿神经元脂褐质沉积症(LINCL)、晚期婴儿Batten病、Janksy-Bielschowsky病,和三肽肽酶1(TPP1)缺乏症,是由CLN2基因突变引起的一种致命的儿童常染色体隐性神经退行性溶酶体贮积症。

该病影响中枢神经系统(CNS)和视网膜,典型发病年龄为2~4岁。临床过程的特点是进行性神经衰弱,伴有认知障碍、视力衰竭、癫痫发作、运动和语言能力恶化,患儿一般在10~12岁时死亡。

该病是由CLN2基因突变引起的,该基因编码溶酶体TPP1,是一种降解溶酶体的多肽N端的酶。TPP1活性的丧失导致溶酶体中储存物质的积累,光镜下表现为带有自体荧光的细胞内沉积物的聚积。

最近,研究人员在一项非随机试验中测试了AAVrh.10hCLN2(一种编码人CLN2的非人血清型rh.10腺相关病毒载体)的脑内递送,该试验由两个臂组成,评估时间为18个月。

试验包括AAVrh.10hCLN2治疗的8名轻度至中度疾病儿童队列,以及由12名儿童组成的未经治疗的威尔-康奈尔自然史队列。治疗后的队列还与一个未治疗的CLN2疾病的欧洲自然史队列进行了比较。

在没有免疫抑制的情况下,通过6个毛刺孔直接向大脑的12个部位注射载体。在另一个方案下的额外安全性评估中,5名患有严重CLN2疾病的儿童接受了AAVrh.10hCLN2治疗。该疗法与各种预期的不良事件相关,没有一个造成长期残疾。系统性抗AAVrh.10免疫的诱导是温和的。

治疗后,治疗队列中脑脊液TPP1增加1.3~2.6倍。与魏尔-康奈尔自然史队列(P<0.04)和欧洲自然史队列(P<0.0001)相比,7名儿童中的4名儿童的灰质体积丢失较慢,运动和语言功能下降率分别降低42.4和47.5%。AAVrh.10hCLN2的脑内给药可延缓CLN2病患儿的疾病进展。

然而,要利用基因疗法阻止疾病进展,我们还需要改进载体设计和递送策略。

 

原始出处:

Dolan Sondhi et al. Slowing late infantile Batten disease by direct brain parenchymal administration of a rh.10 adeno-associated virus expressing CLN2. Science Translational Medicine (2020). 

 

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    希望有更多的技术帮助更多的患者

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1667080, encodeId=34c0166e0807c, content=<a href='/topic/show?id=93d7951895b' target=_blank style='color:#2F92EE;'>#遗传疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95189, encryptionId=93d7951895b, topicName=遗传疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8bd226091152, createdName=lvliquan, createdTime=Sun May 23 20:23:54 CST 2021, time=2021-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2016755, encodeId=ecad2016e5540, content=<a href='/topic/show?id=75a2228481a' target=_blank style='color:#2F92EE;'>#临床数据#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22848, encryptionId=75a2228481a, topicName=临床数据)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fa4f352, createdName=chenlianhui, createdTime=Wed Apr 07 00:23:54 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=917547, encodeId=d27e91e54759, content=希望有更多的技术帮助更多的患者, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210117/611f7350e4ee488fb337d51da5f7b017/1b215c8faadb472ca8e50a2628ff5d8c.jpg, createdBy=1e574842068, createdName=995459620, createdTime=Sun Jan 17 20:27:23 CST 2021, time=2021-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1657388, encodeId=e889165e38867, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, 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=Mon Sep 20 23:23:54 CST 2021, time=2021-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271875, encodeId=5b6912e187521, content=<a href='/topic/show?id=9fef169483' target=_blank style='color:#2F92EE;'>#AAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1694, encryptionId=9fef169483, topicName=AAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8ba7103, createdName=xuqianhua, createdTime=Sun Dec 06 05:23:54 CST 2020, time=2020-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1610815, encodeId=24811610815f6, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, 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 Dec 06 05:23:54 CST 2020, time=2020-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=905215, encodeId=681a905215f2, content=<a href='/topic/show?id=46ce580e865' target=_blank style='color:#2F92EE;'>#新冠肺炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58078, encryptionId=46ce580e865, topicName=新冠肺炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fbc45433548, createdName=ms5000001266883663, createdTime=Sat Dec 05 17:10:43 CST 2020, time=2020-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=905122, encodeId=e780905122d0, content=言简意赅,特别受用, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201204/049b07eb9838407a9de80d92834eede1/04596ea802e342bfaba196f9604cb91c.jpg, createdBy=11325430649, createdName=ms3000001340106445, createdTime=Sat Dec 05 09:57:32 CST 2020, time=2020-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=904872, encodeId=2c169048e276, content=有点前沿性的技术啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, 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=Fri Dec 04 15:16:24 CST 2020, time=2020-12-04, status=1, ipAttribution=)]
    2021-09-20 bsmagic9140
  5. [GetPortalCommentsPageByObjectIdResponse(id=1667080, encodeId=34c0166e0807c, content=<a href='/topic/show?id=93d7951895b' target=_blank style='color:#2F92EE;'>#遗传疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95189, encryptionId=93d7951895b, topicName=遗传疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8bd226091152, createdName=lvliquan, createdTime=Sun May 23 20:23:54 CST 2021, time=2021-05-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2016755, encodeId=ecad2016e5540, content=<a href='/topic/show?id=75a2228481a' target=_blank style='color:#2F92EE;'>#临床数据#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22848, encryptionId=75a2228481a, topicName=临床数据)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fa4f352, createdName=chenlianhui, createdTime=Wed Apr 07 00:23:54 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=917547, encodeId=d27e91e54759, content=希望有更多的技术帮助更多的患者, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210117/611f7350e4ee488fb337d51da5f7b017/1b215c8faadb472ca8e50a2628ff5d8c.jpg, createdBy=1e574842068, createdName=995459620, createdTime=Sun Jan 17 20:27:23 CST 2021, time=2021-01-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1657388, encodeId=e889165e38867, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, 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=Mon Sep 20 23:23:54 CST 2021, time=2021-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1271875, encodeId=5b6912e187521, content=<a href='/topic/show?id=9fef169483' target=_blank style='color:#2F92EE;'>#AAV#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1694, encryptionId=9fef169483, topicName=AAV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8ba7103, createdName=xuqianhua, createdTime=Sun Dec 06 05:23:54 CST 2020, time=2020-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1610815, encodeId=24811610815f6, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, 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 Dec 06 05:23:54 CST 2020, time=2020-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=905215, encodeId=681a905215f2, content=<a href='/topic/show?id=46ce580e865' target=_blank style='color:#2F92EE;'>#新冠肺炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58078, encryptionId=46ce580e865, topicName=新冠肺炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fbc45433548, createdName=ms5000001266883663, createdTime=Sat Dec 05 17:10:43 CST 2020, time=2020-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=905122, encodeId=e780905122d0, content=言简意赅,特别受用, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201204/049b07eb9838407a9de80d92834eede1/04596ea802e342bfaba196f9604cb91c.jpg, createdBy=11325430649, createdName=ms3000001340106445, createdTime=Sat Dec 05 09:57:32 CST 2020, time=2020-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=904872, encodeId=2c169048e276, content=有点前沿性的技术啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, 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=Fri Dec 04 15:16:24 CST 2020, time=2020-12-04, status=1, ipAttribution=)]
    2020-12-06 xuqianhua
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    2020-12-05 ms3000001340106445

    言简意赅,特别受用

    0

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    2020-12-04 易水河

    有点前沿性的技术啊

    0

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超氧化物歧化酶(SOD1)的突变引起肌萎缩侧索硬化症(ALS),这是一种神经退行性疾病,其特征在于上运动神经元和下运动神经元的丧失。

Arthritis Rheumatol:抗中性粒细胞胞浆抗体相关性血管炎的皮肤表现

皮肤表现在AAV中很常见且有差异。在GAV、EGPA、胞浆/抗PR3 ANCA阳性或ANCA阴性患者中,皮肤表现与疾病严重程度相关。

SCI ADV:AAV基因疗法可解决骨关节炎和肥胖问题

肥胖相关的炎症和肌肉功能的丧失在骨关节炎(OA)的发展中起着关键作用;因此,针对肌肉组织的治疗可能可以为恢复与肥胖相关的代谢和生物力学功能障碍提供新的方法。