Combination brain and systemic injections of AAV provide maximal functional and survival benefits in the Niemann-Pick mouse.

ABSTRACT: Niemann-Pick disease (NPD) is caused by the loss of acid sphingomyelinase (ASM) activity, which results in widespread accumulation of undegraded lipids in cells of the viscera and CNS. In this study, we tested the effect of combination brain and systemic injections of recombinant adeno-associated viral vectors encoding human ASM (hASM) in a mouse model of NPD. Animals treated by combination therapy exhibited high levels of hASM in the viscera and brain, which resulted in near-complete correction of storage throughout the body. This global reversal of pathology translated to normal weight gain and superior recovery of motor and cognitive functions compared to animals treated by either brain or systemic injection alone. Furthermore, animals in the combination group did not generate antibodie

SUBMITTER: Passini MA 

PROVIDER: S-EPMC1874225 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature