1. AAV9-NPC1 significantly ameliorates Purkinje cell death and behavioral abnormalities in mouse NPC disease.
- Author
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Xie C, Gong XM, Luo J, Li BL, and Song BL
- Subjects
- Animals, Brain metabolism, Cell Survival genetics, Dependovirus genetics, Disease Models, Animal, Gene Expression Regulation, Humans, Intracellular Signaling Peptides and Proteins, Locomotion genetics, Lung metabolism, Mice, Myocardium metabolism, Niemann-Pick C1 Protein, Niemann-Pick Disease, Type C pathology, Proteins administration & dosage, Purkinje Cells metabolism, Purkinje Cells pathology, Vesicular Transport Proteins administration & dosage, Vesicular Transport Proteins genetics, Gene Transfer Techniques, Genetic Therapy, Niemann-Pick Disease, Type C genetics, Niemann-Pick Disease, Type C therapy, Proteins genetics
- Abstract
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., (Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.)- Published
- 2017
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