Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors
| Autor: | Jason Heth, Deborah A. Cory-Slechta, Paul M. McCray, Beverly L. Davidson, Howard J. Federoff, Andrew I. Brooks, Julie C. Johnston, Colleen S. Stein, Sybille L. Sauter, Stephanie M. Hughes |
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| Rok vydání: | 2002 |
| Předmět: |
Central Nervous System
Cellular pathology Feline immunodeficiency virus Mucopolysaccharidosis Genetic Vectors Central nervous system Mucopolysaccharidosis VII Immunodeficiency Virus Feline Biology Polymerase Chain Reaction Mice Cognition Central Nervous System Diseases Memory Lysosome Lysosomal storage disease medicine Animals Learning Transgenes Glucuronidase Oligonucleotide Array Sequence Analysis Multidisciplinary Behavior Animal Models Genetic Neurodegeneration Gene Transfer Techniques Brain medicine.disease biology.organism_classification Virology Lysosomal Storage Diseases Mice Inbred C57BL Phenotype medicine.anatomical_structure Commentary Neuroscience |
| Zdroj: | Proceedings of the National Academy of Sciences. 99:6216-6221 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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 beta-glucuronidase were unilaterally injected into the striatum of adult beta-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 beta-glucuronidase into brains of beta-glucuronidase-deficient mice with established impairments in spatial learning and memory, there was dramatic recovery of behavioral function. Cognitive improvement resulting from expression of beta-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 beta-glucuronidase activity in the lysosome, and imparts improvements in plasticity and spatial learning. |
| Databáze: | OpenAIRE |
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