Clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer’s disease:a phaseⅠ/Ⅱclinical trial  

作　　者：Xinyi Xie Qingxiang Song Chengxiang Dai Shishuang Cui Ran Tang Suke Li Jing Chang Ping Li Jintao Wang Jianping Li Chao Gao Hongzhuan Chen Shengdi Chen Rujing Ren Xiaoling Gao Gang Wang 

机构地区：[1]Department of Neurology and Institute of Neurology,Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital,Shanghai,China [2]Department of Pharmacology and Chemical Biology,State Key Laboratory of Oncogenes and Related Genes,Shanghai Universities Collaborative Innovation Center for Translational Medicine,Shanghai Jiao Tong University School of Medicine,Shanghai,China [3]Department of Regenerative Medicine Business,Cellular Biomedicine Group,Shanghai,China [4]Daxing Research Institute,University of Science and Technology,Beijing,China [5]Shanghai Frontiers Science Center of TCM Chemical Biology,Institute of Interdisciplinary Integrative Medicine Research,Shanghai University of Traditional Chinese Medicine,Shanghai,China

出　　处：《General Psychiatry》2023年第5期350-360,共11页综合精神医学（英文）

基　　金：supported by the Ministry of Science and Technology of the People's Republic of China(2021ZD0201804,GW);National Natural Science Foundation of China(92068111,81973272,XG,81903582,QS);Natural Science Foundation of Shanghai(219ZR1431500,GW);Shanghai Science and Technology Committee(121XD1422200,XG)and Cellular Biomedicine Group(CBMG,Shanghai,China).

摘　　要：Background There have been no effective treatments for slowing or reversing Alzheimer’s disease(AD)until now.Growing preclinical evidence,including this study,suggests that mesenchymal stem cells-secreted exosomes(MSCs-Exos)have the potential to cure AD.Aims The first three-arm,drug-intervention,phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos(ahaMSCs-Exos)in patients with mild to moderate AD.Methods The eligible subjects were assigned to one of three dosage groups,intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks,and underwent follow-up visits at weeks 16,24,36 and 48.Results No adverse events were reported.In the medium-dose arm,Alzheimer’s Disease Assessment Scale–Cognitive section(ADAS-cog)scores decreased by 2.33(1.19)and the basic version of Montreal Cognitive Assessment scores increased by 2.38(0.58)at week 12 compared with baseline levels,indicating improved cognitive function.Moreover,the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week 36.There were no significant differences in altered amyloid or tau deposition among the three arms,but hippocampal volume shrank less in the medium-dose arm to some extent.Conclusions Intranasal administration of ahaMSCs-Exos was safe and well tolerated,and a dose of at least 4×10^(8)particles could be selected for further clinical trials.

关 键 词：clinical Alzheimer DOSAGE 

分 类 号：R749.16[医药卫生—神经病学与精神病学]