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- Title
Adeno-associated Virus Type 5 Reduces Learning Deficits and Restores Glutamate Receptor Subunit Levels in MPS VII Mice CNS.
- Authors
Liu, Gumei; Yong Hong Chen; Xiaohua He; Martins, Inês; Heth, Jason A.; Chiorini, John A.; Davidson, Beverly L.
- Abstract
A major challenge in treating lysosomal storage diseases with enzyme therapy is correcting symptoms in the central nervous system (CNS). This study used a murine model of mucopolysaccharidosis type VII (MPS VII) to test whether pathological and functional CNS defects could be corrected by expressing β-glucuronidase via bilateral intrastriatal injection of adeno-associated virus type 5 (AAV5βgluc) vectors. After injecting AAV5βgluc, different brain regions expressed active β-glucuronidase, which corrected lysosomal storage defects. Compared to age-matched littermates, adult MPS VII mice were impaired in spatial learning and memory, as measured by the repeated acquisition and performance chamber (RAPC) assay. AAV5βgluc-treated MPS VII mice improved significantly in the RAPC assay, relative to saline-injected littermates. Moreover, our studies reveal that cognitive changes in MPS VII mice correlate with decreased N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor expression. Importantly, AAV5βgluc delivery restored glutamate receptor levels. Together, these data demonstrate that AAV5 vectors deliver a therapeutically effective β-glucuronidase gene to the CNS and further suggest a possible mechanism underlying spatial learning defects in MPS VII mice.Molecular Therapy (2007) 15, 242–247. doi:10.1038/sj.mt.6300016
- Subjects
THERAPEUTICS; LYSOSOMAL storage diseases; THERAPEUTIC use of enzymes; CENTRAL nervous system; MUCOPOLYSACCHARIDOSIS; GLUCURONIDASE; ADENOVIRUSES; LABORATORY mice
- Publication
Molecular Therapy, 2007, Vol 15, Issue 2, p242
- ISSN
1525-0016
- Publication type
Article
- DOI
10.1038/sj.mt.6300016