出版社：American Society for Biochemistry and Molecular Biology
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.
关键词：cholesterol ; gene therapy ; Niemann-Pick type C disease ; lysosomal storage diseases ; adeno-associated virus serotype 9 ; Niemann-Pick type C1 ; blood-brain barrier
