Abstract | BACKGROUND: METHODS: RESULTS: Six months after gene delivery, bladder distension was prevented in all treated animals, and behavioural deficits were improved. Therapeutic enzyme activity from the most efficacious vector, which was also the simpler vector, ranged from 0.5- to four-fold normal within the brains of treated animals, and the average amount of integrated vector ranged from 0.1-1 gene copies per cell. Consequently, levels of ganglioside and lysosomal β- hexosaminidase, both of which are characteristically elevated in MPS IIIA, were significantly reduced, or were normalised. CONCLUSIONS: The present study demonstrates the efficacy of the intraventricular injection as a tool to target the brain with therapeutic genes in adult MPS IIIA mice, and provides evidence supporting this approach as a potentially effective means of treating CNS pathology in MPS IIIA patients.
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Authors | Chantelle McIntyre, Ainslie L K Derrick-Roberts, Sharon Byers, Donald S Anson |
Journal | The journal of gene medicine
(J Gene Med)
2014 Nov-Dec
Vol. 16
Issue 11-12
Pg. 374-87
ISSN: 1521-2254 [Electronic] England |
PMID | 25418946
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 John Wiley & Sons, Ltd. |
Chemical References |
- G(M3) Ganglioside
- G(M2) Ganglioside
- Hydrolases
- N-sulfoglucosamine sulfohydrolase
- beta-N-Acetylhexosaminidases
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Topics |
- Animals
- Brain
(enzymology, pathology)
- G(M2) Ganglioside
(metabolism)
- G(M3) Ganglioside
(metabolism)
- Genetic Therapy
- Humans
- Hydrolases
(biosynthesis, genetics)
- Injections, Intraventricular
- Lentivirus
(genetics)
- Male
- Maze Learning
- Mice
- Mucopolysaccharidosis III
(psychology, therapy)
- Transduction, Genetic
- Treatment Outcome
- beta-N-Acetylhexosaminidases
(biosynthesis, genetics)
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