Lancet：采用干细胞进行免疫系统再造，有望治愈多发性硬化

2016-06-18 MedSci MedSci原创

渥太华大学及医学院的两名研究人员经过多年的潜心研究，现在已经找到治疗多发性硬化症的方法。他们的学术成果报告刊登在6月份的《手术刀》国际医学期刊上。这是马克·弗里德曼（Mark S. Freedman）医生与他的同事哈里·阿特金斯（ Harry Atkins）博士不懈努力取得的突破性成果。多发性硬化症（Multiple Sclerosis）是一种慢性、炎症性中枢神经系统疾病，严重时可以导致活

加拿大渥太华大学医学院的两名研究人员经过多年的研究发现一种潜在治疗多发性硬化症的方法。研究成果刊登在6月份的《柳叶刀》(Lancet）上。研究主要由马克·弗里德曼（Mark S. Freedman）医生与他的同事哈里·阿特金斯（ Harry Atkins）博士完成。

多发性硬化症（Multiple Sclerosis，MS）是一种慢性、炎症性中枢神经系统疾病，严重时可以导致活动性障碍和残疾。因为它影响神经元传递的信息，逐渐造成大脑和脊髓的斑块性的神经髓鞘的破坏，造成多部位的僵硬或丧失功能。此病的平均发病年龄一般在20至40岁，女性发病人数多于男性。目前缺少有效治疗药物。

弗里德曼和阿特金斯医生从13年前就开始用免疫系统再造疗法治疗多发性硬化症患者。他解释说：“这种办法是先清除患者体内的免疫系统（清髓治疗），然后注入用患者血液中的干细胞培养出的新免疫系统”。

这项临床2期单臂研究在加拿大三家医院中进行。招募18-50岁的预后不佳的多发性硬化患者，这些患者处于疾病进展状态，而且EDSS分级（Expanded Disability Status Scale）在3.0-6.0之间。自体CD34细胞从造血干细胞经过环磷酰胺和GM-CSF刺激后收集。患者免疫耗竭采用白消安，环磷酰胺和兔抗胸腺细胞球蛋白，然后进行 aHSCT。主要终点为多发性硬化无活动生存时间。研究方案在www.clinicaltrials.gov/show/NCT02239393

在诊断和aHSCT之间，24例患者有167次临床复发，超过140人年。中位随访6.7年（3.9-12.7年）。主要终点方面，多发性硬化3年无活动生存率为69.6%（95%CI：46.6-84.2）。最长随访13年，没有出现复发。其中一例死于移植相关并发症。35%患者EDSS持续改善。

研究采用骨髓间充质干细胞（Mesenchymal stem cells,MSCs），能够调节患者的免疫功能，减少炎症反应。Freedman 说之所以采用MSCs，主要看重它的抗炎作用。但是，Freedman 也解释说，目前我们还不知道其中的作用机制。他把这项研究称为MESCAMS ("MEsenchymal Stem cell therapy for CAnadian MS patients")。

在这项研究中，期间一名患者因移植的相关并发症而死亡，主要原因是肝衰，使他们意识到可能是因为新的免疫系统给肝脏带来了过重的解毒负担。此后他们就研究如何减少干细胞治疗时的不良反应。

“从那以后，就再也没有发生移植带来较高毒性的问题，没有复发患者，也没有一例再检测到因活动性炎症带来的脑损伤，没有一名患者需要再服用控制硬化症的药物。近70％的患者都是多发性硬化症在他们身上完全消失”。

Drs. Harry Atkins and Mark Freedman of The Ottawa Hospital

渥太华医院治疗多样硬化症成功的案例使世界各地患有此病的人看到了希望。很多人都给渥太华的医生和研究人员写信、发邮件，希望得到同样的治疗。弗里德曼说，全世界大约230万名多发性硬化症患者，其中加拿大有约10万人。现在他们几乎每天收到患者或家属的信件或邮件。甚至有一个比较富裕的人还提议再建一个新的治疗中心。

但是弗里德曼说，很遗憾我们不能为世界各地的患者提供治疗。“因为我们不是营业性的医院。我们的工作是帮助加拿大的患者。我们的卫生保健系统将不允许我们接收来自世界各地的病人”。

渥太华医学研究人员使用免疫系统再造的方法治疗多发性硬化症，第一个阶段的实验总共花费了 670万加元，这些资金是加拿大“多发性硬化症联合会”及附属的基金会提供的。

原始出处：

Atkins HL, Bowman M, Allan D, Anstee G, Arnold DL, Bar-Or A, Bence-Bruckler I, Birch P, Bredeson C, Chen J, Fergusson D, Halpenny M, Hamelin L, Huebsch L, Hutton B, Laneuville P, Lapierre Y, Lee H, Martin L, McDiarmid S, O'Connor P, Ramsay T, Sabloff M, Walker L, Freedman MS. Immunoablation and autologous haemopoietic stem-cell transplantation for aggressive multiple sclerosis: a multicentre single-group phase 2 trial. Lancet. 2016 Jun 8. pii: S0140-6736(16)30169-6.

Saccardi R, Freedman MS, Sormani MP, Atkins H, Farge D, Griffith LM, Kraft G, Mancardi GL, Nash R, Pasquini M, Martin R, Muraro PA; European Blood and Marrow Transplantation Group; Center for International Blood and Marrow Research; HSCT in MS International Study Group. A prospective, randomized, controlled trial of autologous haematopoietic stem cell transplantation for aggressive multiple sclerosis: a position paper. Mult Scler. 2012 Jun;18(6):825-34

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2017-01-20 howi

#Lancet#

66 0
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2017-01-21 jml2009

#多发性#

54 0
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2016-07-10 oo902

太厉害啦

122 0
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2016-06-19 hl573567

这个厉害啊，要是通过肝细胞通过自身免疫治愈肿瘤就更剽悍了。

142 0
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2016-06-19 milkshark

这个厉害

155 0
[GetPortalCommentsPageByObjectIdResponse(id=1828523, encodeId=b48518285235c, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Fri Jan 20 21:54:00 CST 2017, time=2017-01-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1889679, encodeId=19b818896e90a, content=<a href='/topic/show?id=760c430895a' target=_blank style='color:#2F92EE;'>#多发性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43089, encryptionId=760c430895a, topicName=多发性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04d6114, createdName=jml2009, createdTime=Sat Jan 21 04:54:00 CST 2017, time=2017-01-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=92526, encodeId=022392526e3, content=太厉害啦, beContent=null, objectType=article, channel=null, level=null, likeNumber=122, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Sun Jul 10 09:11:00 CST 2016, time=2016-07-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=90545, encodeId=44da905458e, content=这个厉害啊，要是通过肝细胞通过自身免疫治愈肿瘤就更剽悍了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=142, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160611/IMG575BDDE29B42C3218.jpg, createdBy=5c861626135, createdName=hl573567, createdTime=Sun Jun 19 18:04:00 CST 2016, time=2016-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=90499, encodeId=5f49904999a, content=这个厉害, beContent=null, objectType=article, channel=null, level=null, likeNumber=155, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7cde98330, createdName=milkshark, createdTime=Sun Jun 19 06:24:00 CST 2016, time=2016-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=90500, encodeId=7aba90500f9, content=的确很牛, beContent=null, objectType=article, channel=null, level=null, likeNumber=131, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7cde98330, createdName=milkshark, createdTime=Sun Jun 19 06:24:00 CST 2016, time=2016-06-19, status=1, ipAttribution=)]
2016-06-19 milkshark

的确很牛

131 0

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