清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome.

作者
Bernhard Gentner,Francesca Tucci,Stefania Galimberti,Francesca Fumagalli,Maurizio De Pellegrin,Paolo Silvani,Chiara Camesasca,Silvia Pontesilli,Silvia Darin,Francesca Ciotti,Marina Sarzana,Giulia Consiglieri,Chiara Filisetti,Giulia Forni,Laura Passerini,Daniela Tomasoni,Daniela Cesana,Andrea Calabria,Giulio Spinozzi,M. P. Cicalese,Valeria Calbi,Maddalena Migliavacca,Federica Barzaghi,Francesca Ferrua,Vera Gallo,Simona Miglietta,Erika Zonari,Patali S Cheruku,Claudia Forni,Marcella Facchini,Ambra Corti,Michela Gabaldo,Stefano Zancan,Serena Gasperini,Attilio Rovelli,Jaap-Jan Boelens,Simon Jones,Robert Wynn,Cristina Baldoli,Eugenio Montini,Silvia Gregori,Fabio Ciceri,Maria Grazia Valsecchi,Giancarlo la Marca,Rossella Parini,Luigi Naldini,Alessandro Aiuti,Maria-Ester Bernardo
出处
期刊:The New England Journal of Medicine [Massachusetts Medical Society]
卷期号:385 (21): 1929-1940 被引量:5
标识
DOI:10.1056/nejmoa2106596
摘要

Background Allogeneic hematopoietic stem-cell transplantation is the standard of care for Hurler syndrome (mucopolysaccharidosis type I, Hurler variant [MPSIH]). However, this treatment is only partially curative and is associated with complications. Methods We are conducting an ongoing study involving eight children with MPSIH. At enrollment, the children lacked a suitable allogeneic donor and had a Developmental Quotient or Intelligence Quotient score above 70 (i.e., none had moderate or severe cognitive impairment). The children received autologous hematopoietic stem and progenitor cells (HSPCs) transduced ex vivo with an α-L-iduronidase (IDUA)-encoding lentiviral vector after myeloablative conditioning. Safety and correction of blood IDUA activity up to supraphysiologic levels were the primary end points. Clearance of lysosomal storage material as well as skeletal and neurophysiological development were assessed as secondary and exploratory end points. The planned duration of the study is 5 years. Results We now report interim results. The children's mean (±SD) age at the time of HSPC gene therapy was 1.9±0.5 years. At a median follow-up of 2.10 years, the procedure had a safety profile similar to that known for autologous hematopoietic stem-cell transplantation. All the patients showed prompt and sustained engraftment of gene-corrected cells and had supraphysiologic blood IDUA activity within a month, which was maintained up to the latest follow-up. Urinary glycosaminoglycan (GAG) excretion decreased steeply, reaching normal levels at 12 months in four of five patients who could be evaluated. Previously undetectable levels of IDUA activity in the cerebrospinal fluid became detectable after gene therapy and were associated with local clearance of GAGs. Patients showed stable cognitive performance, stable motor skills corresponding to continued motor development, improved or stable findings on magnetic resonance imaging of the brain and spine, reduced joint stiffness, and normal growth in line with World Health Organization growth charts. Conclusions The delivery of HSPC gene therapy in patients with MPSIH resulted in extensive metabolic correction in peripheral tissues and the central nervous system. (Funded by Fondazione Telethon and others; ClinicalTrials.gov number, NCT03488394; EudraCT number, 2017-002430-23.).
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
tmobiusx完成签到,获得积分10
8秒前
mc完成签到 ,获得积分10
9秒前
我要读博士完成签到 ,获得积分10
23秒前
辣小扬完成签到 ,获得积分10
24秒前
30秒前
gwbk完成签到,获得积分10
38秒前
jozz完成签到 ,获得积分10
46秒前
HCCha完成签到,获得积分10
47秒前
badgerwithfisher完成签到,获得积分10
57秒前
段誉完成签到 ,获得积分10
1分钟前
虞无声完成签到,获得积分10
1分钟前
1分钟前
雪妮完成签到 ,获得积分10
1分钟前
fogsea完成签到,获得积分0
1分钟前
apckkk完成签到 ,获得积分10
1分钟前
冰霜雨露完成签到 ,获得积分10
1分钟前
缥缈的闭月完成签到,获得积分10
2分钟前
六一完成签到 ,获得积分10
2分钟前
怡然的煜城完成签到 ,获得积分10
2分钟前
2分钟前
玄之又玄完成签到,获得积分10
2分钟前
Evangeline993完成签到 ,获得积分10
2分钟前
可飞完成签到,获得积分10
3分钟前
绿色心情完成签到 ,获得积分10
3分钟前
飞翔的企鹅完成签到,获得积分10
3分钟前
wBw完成签到,获得积分10
3分钟前
zhangsan完成签到,获得积分10
3分钟前
3分钟前
TheaGao完成签到 ,获得积分10
4分钟前
高海龙完成签到 ,获得积分10
4分钟前
aldehyde应助哥哥采纳,获得10
4分钟前
程小柒完成签到 ,获得积分10
4分钟前
复杂的听白给复杂的听白的求助进行了留言
4分钟前
如意如意按我心意完成签到 ,获得积分10
4分钟前
碗碗豆喵完成签到 ,获得积分10
4分钟前
科研通AI2S应助科研通管家采纳,获得10
4分钟前
科研通AI2S应助科研通管家采纳,获得10
4分钟前
alanbike完成签到,获得积分10
4分钟前
Santiago完成签到,获得积分10
4分钟前
哥哥完成签到,获得积分10
4分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3968521
求助须知:如何正确求助?哪些是违规求助? 3513358
关于积分的说明 11167301
捐赠科研通 3248700
什么是DOI,文献DOI怎么找? 1794453
邀请新用户注册赠送积分活动 875030
科研通“疑难数据库(出版商)”最低求助积分说明 804664