Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors

Andrew I Brooks; Colleen S Stein; Stephanie M Hughes; Jason Heth; Paul M McCray; Sybille L Sauter; Julie C Johnston; Deborah A Cory-Slechta; Howard J Federoff; Beverly L Davidson

doi:10.1073/pnas.082011999

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Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors

Journal article

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Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors

Andrew I Brooks, Colleen S Stein, Stephanie M Hughes, Jason Heth, Paul M McCray, Sybille L Sauter, Julie C Johnston, Deborah A Cory-Slechta, Howard J Federoff and Beverly L Davidson

Proceedings of the National Academy of Sciences - PNAS, Vol.99(9), pp.6216-6221

From the Cover

04/30/2002

DOI: 10.1073/pnas.082011999

PMCID: PMC122929

PMID: 11959904

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Abstract

Gene transfer vectors based on lentiviruses can transduce terminally differentiated cells in the brain; however, their ability to reverse established behavioral deficits in animal models of neurodegeneration has not previously been tested. When recombinant feline immunodeficiency virus (FIV)-based vectors expressing β-glucuronidase were unilaterally injected into the striatum of adult β-glucuronidase deficient [mucopolysaccharidosis type VII (MPS VII)] mice, an animal model of lysosomal storage disease, there was bihemispheric correction of the characteristic cellular pathology. Moreover, after the injection of FIV-based vectors expressing β-glucuronidase into brains of β-glucuronidase-deficient mice with established impairments in spatial learning and memory, there was dramatic recovery of behavioral function. Cognitive improvement resulting from expression of β-glucuronidase was associated with alteration in expression of genes associated with neuronal plasticity. These data suggest that enzyme replacement to the MPS VII central nervous system goes beyond restoration of β-glucuronidase activity in the lysosome, and imparts improvements in plasticity and spatial learning.

Biological Sciences

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Title: Subtitle: Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors
Creators: Andrew I Brooks - Departments of
Colleen S Stein - Departments of
Stephanie M Hughes - Departments of
Jason Heth - Departments of
Paul M McCray - Departments of
Sybille L Sauter - Departments of
Julie C Johnston - Departments of
Deborah A Cory-Slechta - Departments of
Howard J Federoff - Departments of
Beverly L Davidson - Departments of
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.99(9), pp.6216-6221
Series: From the Cover
DOI: 10.1073/pnas.082011999
PMID: 11959904
PMCID: PMC122929
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 04/30/2002
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
Record Identifier: 9984093310802771

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