Source:http://linkedlifedata.com/resource/pubmed/id/15996520
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2005-8-15
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| pubmed:abstractText |
Globoid-cell leukodystrophy (GLD) is an autosomal recessive lysosomal storage disorder caused by mutations in the galactosylceramidase (GALC) gene. Infantile GLD has a lethal course with severe cerebral demyelination that progresses to death by 2 years of age. In the current study twitcher mice, an authentic murine model of infantile GLD, were given intracranial injections of either recombinant adeno-associated virus serotype 2 encoding the murine Galc cDNA (AAV2-GALC) or the same genome pseudotyped with AAV5 capsid proteins (AAV2/5-GALC) on day 3 of age. The group injected intracranially with AAV2/5-GALC had approximately 25-fold greater than normal Galc levels in the brain, while AAV2-GALC-injected animals had 28% normal levels. The average life expectancy of twitcher mice ( approximately 38 days) was significantly (P < 0.0001) increased to 48 and 52 days for the AAV2-GALC- and AAV2/5-GALC-treated groups, respectively. The AAV2/5-GALC group performed significantly better in a battery of behavioral tests compared to untreated, AAV2-GFP-treated, or AAV2-treated twitcher animals. This longitudinal study demonstrated that AAV2/5-GALC-mediated gene therapy resulted in higher levels of Galc expression and slowed the neurologic deterioration more completely than AAV2-GALC in the murine model of globoid-cell leukodystrophy. However, the clinical improvements, as assessed by behavioral tests and life span, were only modest.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Sep
|
| pubmed:issn |
1525-0016
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
12
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
422-30
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:15996520-Animals,
pubmed-meshheading:15996520-Behavior, Animal,
pubmed-meshheading:15996520-Body Weight,
pubmed-meshheading:15996520-Brain,
pubmed-meshheading:15996520-Central Nervous System Diseases,
pubmed-meshheading:15996520-DNA, Complementary,
pubmed-meshheading:15996520-Dependovirus,
pubmed-meshheading:15996520-Disease Models, Animal,
pubmed-meshheading:15996520-Galactosylceramidase,
pubmed-meshheading:15996520-Gene Therapy,
pubmed-meshheading:15996520-Gene Transfer Techniques,
pubmed-meshheading:15996520-Genetic Vectors,
pubmed-meshheading:15996520-Genotype,
pubmed-meshheading:15996520-Green Fluorescent Proteins,
pubmed-meshheading:15996520-Homozygote,
pubmed-meshheading:15996520-Leukodystrophy, Globoid Cell,
pubmed-meshheading:15996520-Mice,
pubmed-meshheading:15996520-Mutation,
pubmed-meshheading:15996520-Neurons,
pubmed-meshheading:15996520-Phenotype,
pubmed-meshheading:15996520-Polymerase Chain Reaction,
pubmed-meshheading:15996520-Time Factors
|
| pubmed:year |
2005
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| pubmed:articleTitle |
AAV2/5 vector expressing galactocerebrosidase ameliorates CNS disease in the murine model of globoid-cell leukodystrophy more efficiently than AAV2.
|
| pubmed:affiliation |
Department of Internal Medicine, Washington University School of Medicine, Box 8007, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|