title: Bilateral single-site intracerebral injection of a nonpathogenic herpes simplex virus-1 vector decreases anxiogenic behavior in MPS VII mice.
abstract: Genetic diseases of the brain usually have pathologic lesions distributed throughout, thus requiring global correction. Herpes simplex virus-1 (HSV-1) vectors may be especially useful for gene delivery in these disorders since they can spread trans-synaptically along neuronal pathways to distal sites from a localized injection. We have previously shown that a nonpathogenic HSV-1 (strain 1716), which is deleted in the ICP34.5 gene, and expressing the lysosomal enzyme β-glucuronidase (GUSB) from the latency-associated transcript (LAT) promoter, spreads within the brains of GUSB-deficient mucopolysaccharidosis VII mice to reverse the pathognomonic storage lesions throughout the diseased brain. In this study, we tested the ability of the 1716 LAT-GUSB vector to improve behavioral deficits. The treatment significantly decreased anxiogenic behaviors associated with the mutation, as indicated by open-field behavior and decreased neophobia in a novel object-recognition task. The treated mice also exhibited an improvement in cognitive function associated with the cerebral cortex in a familiar object test. The results indicate the functional therapeutic potential of the 1716 LAT-GUSB vector.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
authors.forename: Wenpei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
authors.forename: Gerald
authors.initials: G
authors.lastname: Griffin
authors.affiliation: Stokes Institute, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania, USA.
authors.forename: Trena
authors.initials: T
authors.lastname: Clarke
authors.affiliation: Stokes Institute, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Parente
authors.affiliation: Stokes Institute, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania, USA ; Department of Anesthesiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Valentino
authors.affiliation: Stokes Institute, Children's Hospital of Philadelphia , Philadelphia, Pennsylvania, USA ; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA ; W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Wolfe
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, Pennsylvania, USA.
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Fraser