Linked Life Data

15772092

Source:http://linkedlifedata.com/resource/pubmed/id/15772092

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-4-14
pubmed:abstractText
A deficiency of arylsulfatase A (ASA) causes the lysosomal storage disease metachromatic leukodystrophy, which is characterized by accumulation of the sphingolipid 3-O-sulfogalactosylceramide (sulfatide). Sphingolipid storage results in progressive demyelination and severe neurologic symptoms. The disease is lethal, and curative therapy is not available. To assess the therapeutic potential of enzyme replacement therapy (ERT), ASA knockout mice were treated by intravenous injection of recombinant human ASA. Plasma levels of ASA declined with a half-time of approximately 40 min, and enzyme was detectable in tissues within minutes after injection. The uptake of injected enzyme was high into liver, moderate into peripheral nervous system (PNS) and kidney and very low into brain. The apparent half-life of endocytosed enzyme was approximately 4 days. A single injection led to a time- and dose-dependent decline of the excess sulfatide in PNS and kidney by up to 70%, but no reduction was seen in brain. Four weekly injections with 20 mg/kg body weight not only reduced storage in peripheral tissues progressively, but also were surprisingly effective in reducing sulfatide storage in brain and spinal cord. The histopathology of kidney and central nervous system was ameliorated. Improved neuromotor coordination capabilities and normalized peripheral compound motor action potential demonstrate the benefits of ERT on the nervous system function. Enzyme replacement may therefore be a promising therapeutic option in this devastating disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1139-52
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Enzyme replacement improves nervous system pathology and function in a mouse model for metachromatic leukodystrophy.
pubmed:affiliation
Institut Für Physiologische Chemi, Rheinische Friedrich-Wilhelms Universität, Nussallee 11, 53115 Bonn, Germany. matzner@institut.physiochem.uni-bonn.de
pubmed:publicationType
Journal Article