Abstract |
Sandhoff disease is an autosomal recessive lysosomal disorder due to mutations in the beta-hexosaminidase beta-chain gene, resulting in beta- hexosaminidases A (alphabeta) and B (betabeta) deficiency and GM2 ganglioside accumulation in the brain. In this study, our aim was to demonstrate that transduction of cerebral endothelial cells cultured in two-chamber culture inserts with a lentiviral vector encoding the hexosaminidases alpha and beta chains could induce a vectorial secretion of hexosaminidases. Therefore, the human cerebral endothelial cell line hCMEC/D3 was infected with the bicistronic vector from the apical compartment, and beta-hexosaminidase activity was measured in transduced cells and in deficient fibroblasts co-cultured in the basal (i.e. brain) compartment. Induced beta-hexosaminidase secretion by transduced hCMEC/D3 cells was sufficient to allow for a 70-90% restoration of beta-hexosaminidase activity in deficient fibroblasts. On the basis of these in vitro data, we propose that brain endothelium be considered as a novel therapeutic target in Sandhoff disease.
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Authors | Lionel Batista, Florence Miller, Céline Clave, Audrey Arfi, Gaëlle Douillard-Guilloux, Pierre-Olivier Couraud, Catherine Caillaud |
Journal | Neurobiology of disease
(Neurobiol Dis)
Vol. 37
Issue 3
Pg. 656-60
(Mar 2010)
ISSN: 1095-953X [Electronic] United States |
PMID | 20005954
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | 2009 Elsevier Inc. All rights reserved. |
Chemical References |
- G(M2) Ganglioside
- beta-N-Acetylhexosaminidases
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Topics |
- Cell Line, Transformed
- Cerebral Arteries
(cytology, enzymology)
- Cerebrum
(blood supply, enzymology, physiopathology)
- Coculture Techniques
- Diffusion Chambers, Culture
- Endothelial Cells
(enzymology, metabolism)
- Fibroblasts
(enzymology, metabolism)
- G(M2) Ganglioside
(metabolism)
- Genetic Therapy
(methods)
- Genetic Vectors
(pharmacology, therapeutic use)
- Humans
- Lentivirus
(genetics)
- Sandhoff Disease
(enzymology, genetics, therapy)
- Transduction, Genetic
(methods)
- beta-N-Acetylhexosaminidases
(genetics, metabolism)
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