Skip Navigation



Human Molecular Genetics Advance Access published online on November 25, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi425
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
15/1/53    most recent
ddi425v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Sevin, C.
Right arrow Articles by Cartier, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sevin, C.
Right arrow Articles by Cartier, N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press. All rights reserved
Received October 5, 2005
Accepted November 11, 2005

Article

Intracerebral Adeno-Associated Virus-mediated gene transfer in rapidly progressive forms of metachromatic leukodystrophy

Caroline Sevin 1, Abdellatif Benraiss 1, Debby Van Dam 2, Delphine Bonnin 1, Guy Nagels 3, Lucie Verot 4, Ingrid Laurendeau 5, Michel Vidaud 5, Volkmar Gieselmann 6, Marie Vanier 4, Peter Paul De Deyn 7, Patrick Aubourg 1, and Nathalie Cartier 1 *

1 Institut National de la Santé et de la Recherche Médicale Inserm U561 and Université ParisV, 75014 Paris, France
2 Laboratory of Neurochemistry and Behavior at Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp 1, Antwerp B-2610, Belgium
3 National MS Centre, Melsbroek and Department of Neurology, University Hospital, Edegem, Belgium
4 Inserm and Fondation Gillet-Mérieux, Hôpital Lyon-Sud, 69310 Pierre-Benite, France
5 Laboratoire de Génétique Moléculaire-UPRES EA 3618, Faculté des Sciences Pharmaceutiques, Université Paris V, 75014 Paris, France
6 Institute of Physiological Chemistry, Rheinische Friedrich-Wilhelms-Universität, 53115 Bonn, Germany
7 Laboratory of Neurochemistry and Behavior at Institute Born-Bunge, Department of Biomedical Sciences, University of Antwerp 1, Antwerp B-2610, Belgium; Department of Neurology and Memory Clinic, Middelheim General Hospital, B-2020 Antwerp, Belgium

* To whom correspondence should be addressed.
Nathalie Cartier, E-mail: cartier{at}paris5.inserm.fr


  Abstract

Metachromatic leukodystrophy (MLD) is a neurodegenerative lysosomal disease caused by a defect of the enzyme arylsulfatase A (ARSA) that disrupts the degradation of sulfatides in neurons and glial cells. Therapy for MLD requires active production of ARSA in the brain to prevent demyelination and neuronal damage, and efficient delivery of ARSA to act faster than disease progression, particularly in the rapidly progressive late infantile form. We used an adeno-associated virus serotype 5 (AAV5) vector to express the human ARSA gene in the brain of MLD mouse model. We achieved rapid, extensive and long-lasting expression of the recombinant ARSA in the brain, cerebellum and brainstem from at least 3 to 15 months post-injection. Analysis of the vector genome and ARSA distribution gave evidence for in vivo cross-correction of many untransduced neurons and astrocytes. ARSA delivery rapidly reversed sulfatide storage and prevented neuropathological abnormalities and neuromotor impairment. We believe that AAV5-mediated brain delivery of ARSA is a potentially efficacious therapeutic strategy for MLD patients, especially for those with rapidly progressive form of the disease.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Neurosci.Home page
M. I. Givogri, F. Galbiati, S. Fasano, S. Amadio, L. Perani, D. Superchi, P. Morana, U. Del Carro, S. Marchesini, R. Brambilla, et al.
Oligodendroglial progenitor cell therapy limits central neurological deficits in mice with metachromatic leukodystrophy.
J. Neurosci., March 22, 2006; 26(12): 3109 - 3119.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.