Evaluation of AAV-mediated Gene Therapy for Central @entity16 in @entity235 XXXX .

@entity2315 @entity32 @entity235 @entity16 @entity18644 @entity71167
@entity18644 ( @entity18644 ) is a @entity2315 arising from mutations in b-d-glucuronidase ( @entity71167 ), which results in glycosaminoglycan (GAG) accumulation and a variety of clinical manifestations including @entity16 . Herein, @entity18644 @entity235 were injected intravenously (i.v.) and/or intrathecally (i.t.) via the cisterna magna with AAV9 or AAVrh10 vectors carrying the @entity235 @entity71167 cDNA. Although i.v. injection alone at 3 days of age resulted in normal cerebrospinal fluid (CSF) @entity71167 activity, brain tissue homogenates had only ~1 to 6% normal @entity71167 activity and continued to have elevated GAG storage. In contrast, i.t. injection at 3 weeks of age resulted in CSF @entity71167 activity 44-fold normal while brain tissue homogenates had >100% normal @entity71167 activity and reduced GAGs compared with untreated @entity235 . Markers for secondary storage and @entity32 were eliminated in i.t.-treated @entity235 and reduced in i.v.-treated @entity235 compared with untreated @entity235 . Given that i.t.-treated @entity235 expressed higher levels of @entity71167 in the CNS tissues compared to those treated i.v., we conclude that i.t. injection of AAV9 or AAVrh10 vectors is more effective than i.v. injection alone in the large animal model of @entity18644 .
