title: AAV9-NPC1 significantly ameliorates Purkinje cell death and behavioral abnormalities in mouse NPC disease.
abstract: Niemann-Pick type C (NPC) disease is a fatal inherited neurodegenerative disorder caused by loss-of-function mutations in theNPC1orNPC2gene. There is no effective way to treat NPC disease. In this study, we used adeno-associated virus (AAV) serotype 9 (AAV9) to deliver a functionalNPC1gene systemically intoNPC1-/-mice at postnatal day 4. One single AAV9-NPC1 injection resulted in robust NPC1 expression in various tissues, including brain, heart, and lung. Strikingly, AAV9-mediated NPC1 delivery significantly promoted Purkinje cell survival, restored locomotor activity and coordination, and increased the lifespan ofNPC1-/-mice. Our work suggests that AAV-based gene therapy is a promising means to treat NPC disease.
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Institute for Advanced Studies, Wuhan University, Wuhan 430072, China.|Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Xie
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Xue-Min
authors.initials: XM
authors.lastname: Gong
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Institute for Advanced Studies, Wuhan University, Wuhan 430072, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bo-Liang
authors.initials: BL
authors.lastname: Li
authors.affiliation: Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Institute for Advanced Studies, Wuhan University, Wuhan 430072, China blsong@whu.edu.cn.
authors.forename: Bao-Liang
authors.initials: BL
authors.lastname: Song
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008124:Locomotion / Q000235:genetics; D008168:Lung / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D011506:Proteins / Q000008:administration & dosage / Q000235:genetics*; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology; D033921:Vesicular Transport Proteins / Q000008:administration & dosage / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; C497045:Npc2 protein, mouse; D011506:Proteins; D033921:Vesicular Transport Proteins
keywords: Niemann-Pick type C disease; Niemann-Pick type C1; adeno-associated virus serotype 9; blood-brain barrier; cholesterol; gene therapy; lysosomal storage diseases