标题：Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：9
页码：6216-6221
DOI：10.1073/pnas.082011999
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
