Attenuation of the Niemann-Pick type C2 disease phenotype by intracisternal administration of an AAVrh.10 vector expressing Npc2.

Attenuation of the Niemann-Pick type C2 disease phenotype by intracisternal administration of an AAVrh.10 vector expressing Npc2. Exp Neurol. 2018 Apr 12;: Authors: Markmann S, Reid J, Rosenberg JB, De BP, Kaminsky SM, Crystal RG, Sondhi D Abstract Niemann-Pick type C2 (NPC2) disease is a rare, neurodegenerative disorder caused by mutations in the NPC2 gene, leading to lysosomal accumulation of unesterified cholesterol and other lipids. It is characterized by hepatosplenomegaly, liver dysfunction and severe neurological manifestations, resulting in early death. There is no effective therapy for NPC2 disease. Here, we evaluated the effectiveness of an adeno-associated virus (AAV), serotype rh.10 gene transfer vector expressing the mouse Npc2 gene (AAVrh.10-mNpc2-HA, HA tagged to facilitate analysis) to treat the disease in an Npc2-/- mouse model. A single intracisternal administration of the AAVrh.10-mNpc2-HA to 6 wk. old Npc2-/- mice mediated vector DNA, transgene mRNA and protein expression in brain and other organs. Compared to untreated Npc2-/- mice, AAV-treated Npc2-/- mice demonstrated amelioration of disease pathology in the brain, reduced lysosomal storage, reduced Purkinje cell death, decreased gliosis, and improved performance in behavioral tasks. Treatment-related reduction in serum disease markers was detected early and this effect persisted. Liver and spleen pathology were improved with significant reduction of liver chol...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research