Central nervous system delivery of helper-dependent canine adenovirus corrects neuropathology and behavior in mucopolysaccharidosis type VII mice - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Human Gene Therapy Année : 2014

Central nervous system delivery of helper-dependent canine adenovirus corrects neuropathology and behavior in mucopolysaccharidosis type VII mice

Résumé

Canine adenovirus type 2 vectors (CAV-2) are promising tools to treat global central nervous system (CNS) disorders due to their preferential transduction of neurons and efficient retrograde axonal transport. Here we tested the potential of a helper-dependent CAV-2 vector expressing ss-glucuronidase (HD-RIGIE) in a mouse model of mucopolysaccharidosis type VII (MPS VII), a lysosomal storage disease caused by deficiency in ss-glucuronidase activity. MPS VII leads to glycosaminoglycan accumulation into enlarged vesicles in peripheral tissues and the CNS, resulting in peripheral and neuronal dysfunction. Following intracranial administration of HD-RIGIE, we show long-term expression of ss-glucuronidase that led to correction of neuropathology around the injection site and in distal areas. This phenotypic correction correlated with a decrease in secondary-elevated lysosomal enzyme activity and glycosaminoglycan levels, consistent with global biochemical correction. Moreover, HD-RIGIE-treated mice show significant cognitive improvement. Thus, injections of HD-CAV-2 vectors in the brain allow a global and sustained expression and may have implications for a brain therapy in patients with lysosomal storage disease.

Dates et versions

hal-02191549 , version 1 (23-07-2019)

Identifiants

Citer

L. Ariza, L. Gimenez-Llort, A. Cubizolle, G. Pages, B. Garcia-Lareu, et al.. Central nervous system delivery of helper-dependent canine adenovirus corrects neuropathology and behavior in mucopolysaccharidosis type VII mice. Human Gene Therapy, 2014, 25 (3), pp.199--211. ⟨10.1089/hum.2013.152⟩. ⟨hal-02191549⟩
39 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More