NEJM:谷氨酰胺转胺酶2抑制剂治疗乳糜泻概念验证研究获得成功

2021-07-04 MedSci原创 MedSci原创

谷氨酰胺转胺酶2抑制剂ZED1227可减少乳糜泻患者谷蛋白诱导的十二指肠粘膜损伤

乳糜泻是一种自身免疫相关的小肠炎症,发病率在0.2%到2.0%之间,携带HLA-DQ2和HLA-DQ8基因的遗传易感人群,在摄入小麦和相关谷物麸质后会出现乳糜泻症状,但不绝对。临床上的典型症状包括腹泻、体重减轻和营养不良,非特异性或非典型症状,包括疲劳、排便习惯改变、贫血、骨质疏松或自身免疫性疾病(自身免疫性甲状腺炎和1型糖尿病)。小肠中谷氨酰胺转胺酶2可增强T细胞刺激,导致粘膜损伤,是治疗乳糜泻的潜在靶点。近日研究人员开展为期6周的概念验证研究,考察了ZED1227对乳糜泻的治疗效果。

ZED1227是选择性口服谷氨酰胺转胺酶2抑制剂,研究考察了3个剂量的ZED1227与安慰剂相比,对乳糜泻的治疗效果。成年乳糜泻患者在症状得到控制后,随机接受ZED1227或安慰剂,同时每日服用小麦麸质。研究的主要终点是谷蛋白诱导的粘膜损伤,次要终点包括上皮内淋巴细胞密度、乳糜泻症状指数评分和乳糜泻问卷评分。

10 mg、50mg以及100mg ZED1227组各包含41名患者,安慰剂组包含40名患者,各组各自有35、39、38和30名患者接受了终点十二指肠活检采样。ZED1227治疗可减少谷蛋白诱导的十二指肠粘膜损伤。安慰剂相比,10 mg、50mg以及100mg ZED1227组从基线到第6周绒毛高度/隐窝深度变化比率估计为0.44、0.49和0.48。与安慰剂相比,10 mg、50mg以及100mg ZED1227组每100个上皮细胞内淋巴细胞密度变化差异为-2.7、-4.2以及-9.6个细胞。100mg ZED1227组可改善患者乳糜泻相关症状和生活质量评分。ZED1227最常见的不良事件是头痛、恶心、腹泻、呕吐和腹痛,100mg剂量组皮疹率为8%。

ZED1227治疗对绒毛高度/隐窝深度变化的影响

在本次概念验证研究中,谷氨酰胺转胺酶2抑制剂ZED1227可减少乳糜泻患者谷蛋白诱导的十二指肠粘膜损伤

原始出处:

Detlef Schuppan et al. A Randomized Trial of a Transglutaminase 2 Inhibitor for Celiac Disease. N Engl J Med,July 01,2021.

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    2021-08-20 jklm09
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    2021-07-30 小小医者

    #乳糜泻#终于有药物治疗了!谷氨酰胺转胺酶2抑制剂ZED1227

    0

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    2021-07-04 旺医

    顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1852694, encodeId=ae5518526949c, 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=31, 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=Fri Aug 20 09:30:00 CST 2021, time=2021-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995634, encodeId=6a181995634f6, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28b7142, createdName=liuquan, createdTime=Fri Nov 19 02:30:00 CST 2021, time=2021-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1004005, encodeId=265e100400596, content=<a href='/topic/show?id=24cf236e96e' target=_blank style='color:#2F92EE;'>#乳糜泻#</a>终于有药物治疗了!谷氨酰胺转胺酶2抑制剂ZED1227, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23679, encryptionId=24cf236e96e, topicName=乳糜泻)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=小小医者, createdTime=Fri Jul 30 21:44:36 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1035689, encodeId=a25f1035689b0, content=顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=旺医, createdTime=Sun Jul 04 13:30:00 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996086, encodeId=8e16996086b1, content=实用, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210704/3100429e550544c7a1a998b32f95a4d3/fd7116180f994add9ce31f74e2b3c4cb.jpg, createdBy=3b093591991, createdName=132fcf2cm35暂无昵称, createdTime=Sun Jul 04 13:14:21 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996046, encodeId=ec7a9960460d, content=认真学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=b3545492917, createdName=smart Ren, createdTime=Sun Jul 04 11:23:34 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996034, encodeId=cf47996034bc, content=真厉害啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210704/752be60dd72144fa9143ec01dec1533e/9a4a7fbf898f4d5e998e8ce0fa6fbdd8.jpg, createdBy=17955540853, createdName=想要新生活, createdTime=Sun Jul 04 11:01:01 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996020, encodeId=09bf996020e7, content=已读,真是受益匪浅呀。, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Sun Jul 04 10:45:12 CST 2021, time=2021-07-04, status=1, ipAttribution=)]
    2021-07-04 132fcf2cm35暂无昵称

    实用

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1852694, encodeId=ae5518526949c, 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=31, 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=Fri Aug 20 09:30:00 CST 2021, time=2021-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995634, encodeId=6a181995634f6, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28b7142, createdName=liuquan, createdTime=Fri Nov 19 02:30:00 CST 2021, time=2021-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1004005, encodeId=265e100400596, content=<a href='/topic/show?id=24cf236e96e' target=_blank style='color:#2F92EE;'>#乳糜泻#</a>终于有药物治疗了!谷氨酰胺转胺酶2抑制剂ZED1227, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23679, encryptionId=24cf236e96e, topicName=乳糜泻)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=小小医者, createdTime=Fri Jul 30 21:44:36 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1035689, encodeId=a25f1035689b0, content=顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=旺医, createdTime=Sun Jul 04 13:30:00 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996086, encodeId=8e16996086b1, content=实用, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210704/3100429e550544c7a1a998b32f95a4d3/fd7116180f994add9ce31f74e2b3c4cb.jpg, createdBy=3b093591991, createdName=132fcf2cm35暂无昵称, createdTime=Sun Jul 04 13:14:21 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996046, encodeId=ec7a9960460d, content=认真学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=b3545492917, createdName=smart Ren, createdTime=Sun Jul 04 11:23:34 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996034, encodeId=cf47996034bc, content=真厉害啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210704/752be60dd72144fa9143ec01dec1533e/9a4a7fbf898f4d5e998e8ce0fa6fbdd8.jpg, createdBy=17955540853, createdName=想要新生活, createdTime=Sun Jul 04 11:01:01 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996020, encodeId=09bf996020e7, content=已读,真是受益匪浅呀。, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Sun Jul 04 10:45:12 CST 2021, time=2021-07-04, status=1, ipAttribution=)]
    2021-07-04 smart Ren

    认真学习

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1852694, encodeId=ae5518526949c, 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=31, 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=Fri Aug 20 09:30:00 CST 2021, time=2021-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995634, encodeId=6a181995634f6, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28b7142, createdName=liuquan, createdTime=Fri Nov 19 02:30:00 CST 2021, time=2021-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1004005, encodeId=265e100400596, content=<a href='/topic/show?id=24cf236e96e' target=_blank style='color:#2F92EE;'>#乳糜泻#</a>终于有药物治疗了!谷氨酰胺转胺酶2抑制剂ZED1227, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23679, encryptionId=24cf236e96e, topicName=乳糜泻)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=小小医者, createdTime=Fri Jul 30 21:44:36 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1035689, encodeId=a25f1035689b0, content=顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=旺医, createdTime=Sun Jul 04 13:30:00 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996086, encodeId=8e16996086b1, content=实用, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210704/3100429e550544c7a1a998b32f95a4d3/fd7116180f994add9ce31f74e2b3c4cb.jpg, createdBy=3b093591991, createdName=132fcf2cm35暂无昵称, createdTime=Sun Jul 04 13:14:21 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996046, encodeId=ec7a9960460d, content=认真学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=b3545492917, createdName=smart Ren, createdTime=Sun Jul 04 11:23:34 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996034, encodeId=cf47996034bc, content=真厉害啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210704/752be60dd72144fa9143ec01dec1533e/9a4a7fbf898f4d5e998e8ce0fa6fbdd8.jpg, createdBy=17955540853, createdName=想要新生活, createdTime=Sun Jul 04 11:01:01 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996020, encodeId=09bf996020e7, content=已读,真是受益匪浅呀。, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Sun Jul 04 10:45:12 CST 2021, time=2021-07-04, status=1, ipAttribution=)]
    2021-07-04 想要新生活

    真厉害啊

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1852694, encodeId=ae5518526949c, 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=31, 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=Fri Aug 20 09:30:00 CST 2021, time=2021-08-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995634, encodeId=6a181995634f6, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=28b7142, createdName=liuquan, createdTime=Fri Nov 19 02:30:00 CST 2021, time=2021-11-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1004005, encodeId=265e100400596, content=<a href='/topic/show?id=24cf236e96e' target=_blank style='color:#2F92EE;'>#乳糜泻#</a>终于有药物治疗了!谷氨酰胺转胺酶2抑制剂ZED1227, beContent=null, objectType=article, channel=null, level=null, likeNumber=110, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=23679, encryptionId=24cf236e96e, topicName=乳糜泻)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=小小医者, createdTime=Fri Jul 30 21:44:36 CST 2021, time=2021-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1035689, encodeId=a25f1035689b0, content=顶刊就是顶刊,谢谢梅斯带来这么高水平的研究报道,我们科里同事经常看梅斯,分享梅斯上的信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=旺医, createdTime=Sun Jul 04 13:30:00 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996086, encodeId=8e16996086b1, content=实用, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210704/3100429e550544c7a1a998b32f95a4d3/fd7116180f994add9ce31f74e2b3c4cb.jpg, createdBy=3b093591991, createdName=132fcf2cm35暂无昵称, createdTime=Sun Jul 04 13:14:21 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996046, encodeId=ec7a9960460d, content=认真学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=b3545492917, createdName=smart Ren, createdTime=Sun Jul 04 11:23:34 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996034, encodeId=cf47996034bc, content=真厉害啊, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210704/752be60dd72144fa9143ec01dec1533e/9a4a7fbf898f4d5e998e8ce0fa6fbdd8.jpg, createdBy=17955540853, createdName=想要新生活, createdTime=Sun Jul 04 11:01:01 CST 2021, time=2021-07-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=996020, encodeId=09bf996020e7, content=已读,真是受益匪浅呀。, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Sun Jul 04 10:45:12 CST 2021, time=2021-07-04, status=1, ipAttribution=)]
    2021-07-04 ms5000000518166734

    已读,真是受益匪浅呀。

    0

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