Lentivirus-modified hematopoietic stem cell gene therapy for advanced symptomatic juvenile metachromatic leukodystrophy:a long-term follow-up pilot study  

作　　者：Zhao Zhang Hua Jiang Li Huang Sixi Liu Xiaoya Zhou Yun Cai Ming Li Fei Gao Xiaoting Liang Kam-Sze Tsang Guangfu Chen Chui-Yan Ma Yuet-Hung Chai Hongsheng Liu Chen Yang Mo Yang Xiaoling Zhang Shuo Han Xin Du Ling Chen Wuh-Liang Hwu Jiacai Zhuo Qizhou Lian 

机构地区：[1]Cord Blood Bank,Guangzhou Institute of Eugenics and Perinatology,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou 510623,China [2]State Key Laboratory of Pharmaceutical Biotechnology,Department of Medicine,The University of Hong Kong,Hong Kong SAR 999077,China [3]Department of Haematology,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou 510623,China [4]Department of Hematology and Oncology,Shenzhen Children’s Hospital,Shenzhen 518026,China [5]Department of Haematology,Shenzhen Second People’s Hospital,The First Affiliated Hospital of Shenzhen University,Shenzhen University School of Medicine,Shenzhen University,Shenzhen 518060,China [6]Department of Anatomical and Cellular Pathology,The Chinese University of Hong Kong,Hong Kong SAR 999077,China [7]Department of Paediatrics,Shenzhen Second People’s Hospital,The First Affiliated Hospital of Shenzhen University,Shenzhen University School of Medicine,Shenzhen University,Shenzhen 518060,China [8]Department of Child Neurological Rehabilitation,Maternal&Child Health Hospital,Shenzhen 518000,China [9]Department of Radiology,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou 518026,China [10]Scientific Research Center,The Seventh Affiliated Hospital,Sun Yat-sen University,Shenzhen 518107,China [11]Department of Paediatrics and Medical Genetics,Taiwan University Hospital,Taipei 110024,China [12]Department of Pharmacy,Shenzhen Second People’s Hospital,The First Affiliated Hospital of Shenzhen University,Shenzhen University School of Medicine,Shenzhen University,Shenzhen 518060,China [13]Shenzhen University of Advanced Technology,Key Laboratory of Quantitative Synthetic Biology,Shenzhen Institute of Synthetic Biology,Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China

出　　处：《Protein & Cell》2025年第1期16-27,共12页蛋白质与细胞(英文版)

基　　金：supported in part by Poland Fundacja Siepomaga;JS Foundation (Hong Kong);Shenzhen Li Weibo Charity Foundation;Taiwan Rare Disease Foundation。

摘　　要：Metachromatic leukodystrophy(MLD)is an inherited disease caused by a deficiency of the enzyme arylsulfatase A(ARSA).Lentivirus-modified autologous hematopoietic stem cell gene therapy(HSCGT)has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity.Unfortunately,this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis.Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system,whereas those with early onset infantile MLD die within a few years of symptom onset.We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results.The safety profile of HSCGT was favorable in this long-term follow-up over 9 years.The most common adverse events(AEs)within 2 months of HSCGT were related to busulfan conditioning,and all AEs resolved.No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years.Importantly,to date,patients have maintained remarkably improved ARSA activity with a stable disease state,including increased Functional Independence Measure(FIM)score and decreased magnetic resonance imaging(MRI)lesion score.This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.

关 键 词：HSCGT advanced symptomatic metachromatic leukodystrophy JUVENILE patients safety effcacy 

分 类 号：R741[医药卫生—神经病学与精神病学] R450[医药卫生—临床医学]