Linked Life Data

19699666

Source:http://linkedlifedata.com/resource/pubmed/id/19699666

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-11-9
pubmed:abstractText
Mucopolysaccharidosis type IIIA (MPS IIIA) results from lack of functional sulfamidase (SGSH), a lysosomal enzyme. Its substrate, heparan sulfate, and other secondarily-stored compounds subsequently accumulate primarily within the central nervous system (CNS), resulting in progressive mental deterioration and early death. Presently there is no treatment. As a potential therapeutic strategy, recombinant human sulfamidase (rhSGSH) was administered into the CSF (via the cerebellomedullary cistern) of three adult MPS IIIA dogs either twice with a 4 day interval, or weekly for up to 4 weeks. The dogs were euthanased 24 h post-injection along with one untreated unaffected and two MPS IIIA controls. We have examined the three dimensional pattern of distribution of enzyme in the CNS and its ability to reduce primary substrate storage. High concentrations of rhSGSH protein, with up to 39-fold normal enzyme activity levels were detected within widespread areas of the CNS. RhSGSH protein was also detectable by immunohistochemistry in neurons and glia in all three enzyme-treated dogs. In both weekly-treated dogs, relative levels of a heparan sulfate-derived disaccharide, measured using tandem mass spectrometry, were lower in many brain regions when compared to untreated MPS IIIA controls. A moderately severe meningitis was also present as well as antibodies to rhSGSH in CSF/plasma. These findings demonstrate proof of principle that MPS IIIA can be treated by intracisternal enzyme replacement warranting further experiments in animals tolerant to rhSGSH. This enzyme delivery method may represent a means of treating neuropathology in MPS IIIA and other lysosomal storage disorders affecting the CNS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1096-7206
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
383-92
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Effect of cisternal sulfamidase delivery in MPS IIIA Huntaway dogs--a proof of principle study.
pubmed:affiliation
Lysosomal Diseases Research Unit, Dept. Genetics and Molecular Pathology, SA Pathology, Women's and Children's Hospital, North Adelaide, SA 5006, Australia. Kim.Hemsley@adelaide.edu.au
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't