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Circuit-specific gene therapy reverses core symptoms in a primate Parkinson's disease model

文献类型：期刊论文

作者Chen, Yefei10; Hong, Zexuan9,10; Wang, Jingyi8,10; Liu, Kunlin7,10; Liu, Jing9,10; Lin, Jianbang10; Feng, Shijing10; Zhang, Tianhui6,10; Shan, Liang10; Liu, Taian10
刊名CELL
出版日期2023-11-22
卷号186期号:24页码:5394-+
ISSN号0092-8674
DOI10.1016/j.cell.2023.10.004
通讯作者Bao, Jin(jin.bao@siat.ac.cn) ; Dai, Ji(ji.dai@siat.ac.cn) ; Lu, Zhonghua(zh.lu@siat.ac.cn)
英文摘要Parkinson's disease (PD) is a debilitating neurodegenerative disorder. Its symptoms are typically treated with levodopa or dopamine receptor agonists, but its action lacks specificity due to the wide distribution of dopamine receptors in the central nervous system and periphery. Here, we report the development of a gene therapy strategy to selectively manipulate PD-affected circuitry. Targeting striatal D1 medium spiny neurons (MSNs), whose activity is chronically suppressed in PD, we engineered a therapeutic strategy comprised of a highly efficient retrograde adeno-associated virus (AAV), promoter elements with strong D1-MSN activity, and a chemogenetic effector to enable precise D1-MSN activation after systemic ligand administration. Application of this therapeutic approach rescues locomotion, tremor, and motor skill defects in both mouse and primate models of PD, supporting the feasibility of targeted circuit modulation tools for the treatment of PD in humans.
WOS关键词OPTOGENETIC CONTROL ; LEVODOPA ; DYSKINESIA ; RESPONSES ; NEURONS ; MODULATION ; MONKEYS ; ACCESS ; FUTURE ; MOUSE
资助项目National Natural Science Foundation of China ; Ministry of Science and Technology of China ; Shenzhen Science and Technology Innovation Commission[31871090] ; Shenzhen Science and Technology Innovation Commission[32000730] ; Shenzhen Science and Technology Innovation Commission[81961128019] ; Shenzhen Science and Technology Innovation Commission[32000701] ; Shenzhen Science and Technology Innovation Commission[32071020] ; Shenzhen Science and Technology Innovation Commission[U20A2017] ; Shenzhen Technological Research Center for Primate Translational Medicine grant[2018YFA0801404] ; Shenzhen Technological Research Center for Primate Translational Medicine grant[2019YFA0903803] ; Shenzhen Key Laboratory of Drug Addiction grant[JCYJ202103243001018] ; Shenzhen Key Laboratory of Drug Addiction grant[KQTD20210811090117032] ; Shenzhen Key Laboratory of Drug Addiction grant[JCYJ20190809171003698] ; Shenzhen Key Laboratory of Drug Addiction grant[JCYJ20210324140414039] ; Youth Innovation Promotion Association CAS[F-2021-Z99-504979] ; Chinese Academy of Sciences International Partnership Program[ZDSYS20190902093601675] ; China Postdoctoral Science Foundation[2017120] ; Guangdong Basic and Applied Research Foundation[172644KYSB20170004] ; International Science and Technology Cooperation Base of Guangdong Province[2019M653115] ; [2022A1515010134] ; [2020B1515120014] ; [2019A050505008]
WOS研究方向Biochemistry & Molecular Biology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:001125438900001
源URL[http://119.78.100.183/handle/2S10ELR8/308308]  
专题中国科学院上海药物研究所
通讯作者Bao, Jin; Dai, Ji; Lu, Zhonghua
作者单位1.Emugen Therapeut LLC, Woburn, MA 01801 USA
2.Chinese Acad Sci, Biomed Imaging Sci & Syst Key Lab, Shenzhen 518055, Peoples R China
3.Chinese Acad Sci, Brain Cognit & Brain Dis Inst, Guangdong Prov Key Lab Brain Connectome & Behav, CAS Key Lab Brain Connectome & Manipulat,Shenzhen, Shenzhen 518055, Peoples R China
4.Hubei Univ Med, Biomed Res Inst, Shiyan 442000, Peoples R China
5.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China
6.Xuzhou Med Univ, Res Ctr Biochem & Mol Biol, Jiangsu Key Lab Brain Dis & Bioinformat, Xuzhou 221004, Peoples R China
7.Southern Med Univ, Zhujiang Hosp, Guangdong Prov Key Lab Brain Funct Repair & Regene, Guangzhou 510282, Peoples R China
8.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
9.Sout hern Med Univ, Affiliated Shenzhen Matern & Child Healthcare Hosp, Dept Anesthesiol, Shenzhen 518027, Peoples R China
10.Chinese Acad Sci, Shenzhen Hong Kong Inst Brain Sci, Shenzhen Technol Res Ctr Primate Translat Med, Shenzhen Inst Adv Technol,Shenzhen Key Lab Mol Bio, Shenzhen 518055, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Yefei,Hong, Zexuan,Wang, Jingyi,et al. Circuit-specific gene therapy reverses core symptoms in a primate Parkinson's disease model[J]. CELL,2023,186(24):5394-+.
APA Chen, Yefei.,Hong, Zexuan.,Wang, Jingyi.,Liu, Kunlin.,Liu, Jing.,...&Lu, Zhonghua.(2023).Circuit-specific gene therapy reverses core symptoms in a primate Parkinson's disease model.CELL,186(24),5394-+.
MLA Chen, Yefei,et al."Circuit-specific gene therapy reverses core symptoms in a primate Parkinson's disease model".CELL 186.24(2023):5394-+.

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来源：上海药物研究所

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