Linked Life Data

15336648

Source:http://linkedlifedata.com/resource/pubmed/id/15336648

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2004-8-31
pubmed:abstractText
Mucopolysaccharidosis type VII is a lysosomal storage disease caused by deficiency of the acid hydrolase beta-glucuronidase. MPS VII mice develop progressive lysosomal accumulation of glycosaminoglycans within multiple organs, including the brain. Using this animal model, we investigated whether gene transfer mediated by a recombinant adeno-associated virus (rAAV) type 2 vector is capable of reversing the progression of storage in adult mice. We engineered an rAAV2 vector to carry the murine beta-glucuronidase cDNA under the transcriptional direction of the human elongation factor-1alpha promoter. Intrahepatic administration of this vector in adult MPS VII mice resulted in stable hepatic beta-glucuronidase expression (473 +/- 254% of that found in wild-type mouse liver) for at least 1 year postinjection. There was widespread distribution of vector genomes and beta-glucuronidase within extrahepatic organs. The level of enzyme activity was sufficient to reduce lysosomal storage within the liver, spleen, kidney, heart, lung, and brain. Within selected regions of the brain, neuronal, glial, and perivascular cells had histopathologic evidence of reduced storage. Also, brain alpha-galactosidase and beta-hexosaminidase enzyme levels, secondarily elevated by the storage abnormality, were normalized. These data demonstrate that peripheral administration of an rAAV2 vector in adult MPS VII mice can lead to transgene expression levels sufficient for improvements in both the peripheral and the central manifestations of this disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1525-0016
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
478-91
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Widespread correction of lysosomal storage following intrahepatic injection of a recombinant adeno-associated virus in the adult MPS VII mouse.
pubmed:affiliation
Center for Gene Therapy, Columbus Children's Research Institute, Columbus, OH 43205, USA. sferrat@pediatrics.ohio-state.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural