Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/52684
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dc.contributor.authorHemsley, K.-
dc.contributor.authorLuck, A.-
dc.contributor.authorCrawley, A.-
dc.contributor.authorHassiotis, S.-
dc.contributor.authorBeard, H.-
dc.contributor.authorKing, B.-
dc.contributor.authorRozek, T.-
dc.contributor.authorRozaklis, T.-
dc.contributor.authorFuller, M.-
dc.contributor.authorHopwood, J.-
dc.date.issued2009-
dc.identifier.citationEuropean Journal of Neuroscience, 2009; 29(6):1197-1214-
dc.identifier.issn0953-816X-
dc.identifier.issn1460-9568-
dc.identifier.urihttp://hdl.handle.net/2440/52684-
dc.description.abstractMucopolysaccharidosis type IIIA is a neurodegenerative lysosomal storage disorder characterized by progressive loss of learned skills, sleep disturbance and behavioural problems. Absent or greatly reduced activity of sulphamidase, a lysosomal protein, results in intracellular accumulation of heparan sulphate. Subsequent neuroinflammation and neurodegeneration typify this and many other lysosomal storage disorders. We propose that intra-cerebrospinal fluid protein delivery represents a potential therapeutic avenue for treatment of this and other neurodegenerative conditions; however, technical restraints restrict examination of its use prior to adulthood in mice. We have used a naturally-occurring Mucopolysaccharidosis type IIIA mouse model to determine the effectiveness of combining intravenous protein replacement (1 mg/kg) from birth to 6 weeks of age with intra-cerebrospinal fluid sulphamidase delivery (100 μg, fortnightly from 6 weeks) on behaviour, the level of heparan sulphate-oligosaccharide storage and other neuropathology. Mice receiving combination treatment exhibited similar clinical improvement and reduction in heparan sulphate storage to those only receiving intra-cerebrospinal fluid enzyme. Reductions in micro- and astrogliosis and delayed development of ubiquitin-positive lesions were seen in both groups. A third group of intravenous-only treated mice did not exhibit clinical or neuropathological improvements. Intra-cerebrospinal fluid injection of sulphamidase effectively, but dose-dependently, treats neurological pathology in Mucopolysaccharidosis type IIIA, even when treatment begins in mice with established disease.-
dc.description.statementofresponsibilityKim M. Hemsley, Amanda J. Luck, Allison C. Crawley, Sofia Hassiotis, Helen Beard, Barbara King, Tomas Rozek, Tina Rozaklis, Maria Fuller and John J. Hopwood-
dc.language.isoen-
dc.publisherBlackwell Science Ltd-
dc.source.urihttp://dx.doi.org/10.1111/j.1460-9568.2009.06666.x-
dc.subjectcerebrospinal fluid-
dc.subjectlysosomal storage disorder-
dc.subjectmouse-
dc.subjectneuropathology-
dc.subjectSanfilippo-
dc.titleExamination of intravenous and intra-CSF protein delivery for treatment of neurological disease-
dc.typeJournal article-
dc.identifier.doi10.1111/j.1460-9568.2009.06666.x-
pubs.publication-statusPublished-
dc.identifier.orcidHemsley, K. [0000-0003-1038-9884]-
dc.identifier.orcidFuller, M. [0000-0001-9092-8942]-
Appears in Collections:Aurora harvest 5
Paediatrics publications

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