AAV9-NPC1 significantly ameliorates Purkinje cell death and behavioral abnormalities in mouse NPC disease

Journal of Lipid Research

Xue-Min Gong¹  Chang Xie²  Bo-Liang Li²  Jie Luo³  Bao-Liang Song³ 

[1] Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;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;

关键词: cholesterol;    gene therapy;    Niemann-Pick type C disease;    lysosomal storage diseases;    adeno-associated virus serotype 9;    Niemann-Pick type C1;   

DOI  :  

来源: DOAJ

【 摘 要 】

Niemann-Pick type C (NPC) disease is a fatal inherited neurodegenerative disorder caused by loss-of-function mutations in the NPC1 or NPC2 gene. There is no effective way to treat NPC disease. In this study, we used adeno-associated virus (AAV) serotype 9 (AAV9) to deliver a functional NPC1 gene systemically into NPC1−/− 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 of NPC1−/− mice. Our work suggests that AAV-based gene therapy is a promising means to treat NPC disease.

【 授权许可】

Unknown