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https://hdl.handle.net/2440/52684
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dc.contributor.author | Hemsley, K. | - |
dc.contributor.author | Luck, A. | - |
dc.contributor.author | Crawley, A. | - |
dc.contributor.author | Hassiotis, S. | - |
dc.contributor.author | Beard, H. | - |
dc.contributor.author | King, B. | - |
dc.contributor.author | Rozek, T. | - |
dc.contributor.author | Rozaklis, T. | - |
dc.contributor.author | Fuller, M. | - |
dc.contributor.author | Hopwood, J. | - |
dc.date.issued | 2009 | - |
dc.identifier.citation | European Journal of Neuroscience, 2009; 29(6):1197-1214 | - |
dc.identifier.issn | 0953-816X | - |
dc.identifier.issn | 1460-9568 | - |
dc.identifier.uri | http://hdl.handle.net/2440/52684 | - |
dc.description.abstract | Mucopolysaccharidosis 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.statementofresponsibility | Kim 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.iso | en | - |
dc.publisher | Blackwell Science Ltd | - |
dc.source.uri | http://dx.doi.org/10.1111/j.1460-9568.2009.06666.x | - |
dc.subject | cerebrospinal fluid | - |
dc.subject | lysosomal storage disorder | - |
dc.subject | mouse | - |
dc.subject | neuropathology | - |
dc.subject | Sanfilippo | - |
dc.title | Examination of intravenous and intra-CSF protein delivery for treatment of neurological disease | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1111/j.1460-9568.2009.06666.x | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Hemsley, K. [0000-0003-1038-9884] | - |
dc.identifier.orcid | Fuller, M. [0000-0001-9092-8942] | - |
Appears in Collections: | Aurora harvest 5 Paediatrics publications |
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