| Added by | eric_julien |
|---|---|
| Group name | EquipeEJ |
| Item Type | Journal Article |
| Title | Corrective GUSB transfer to the canine mucopolysaccharidosis VII brain |
| Creator | Cubizolle et al. |
| Author | Aurelie Cubizolle |
| Author | Nicolas Serratrice |
| Author | Nadia Skander |
| Author | Marie-Anne Colle |
| Author | Sandy Ibanes |
| Author | Neus Bayo-Puxan |
| Author | Khalil Mazouni |
| Author | Franck Mennechet |
| Author | Beatrice Joussemet |
| Author | Yan Cherel |
| Author | Yaouen Lajat |
| Author | Charles Vite |
| Author | Florence Bernex |
| Author | Vasiliki Kalatzis |
| Author | Mark E. Haskins |
| Author | Eric J. Kremer |
| Abstract | Severe deficiency in lysosomal ?-glucuronidase (?-glu) enzymatic activity results in mucopolysaccharidosis (MPS) VII, an orphan disease with symptoms often appearing in early childhood. Symptoms are variable, but many patients have multiple organ disorders including neurological defects. At the cellular level, deficiency in ?-glu activity leads to abnormal accumulation of glycosaminoglycans (GAGs), and secondary accumulation of GM2 and GM3 gangliosides, which have been linked to neuroinflammation. There have been encouraging gene transfer studies in the MPS VII mouse brain, but this is the first study attempting the correction of the >200-fold larger and challenging canine MPS VII brain. Here, the efficacy of a helper-dependent (HD) canine adenovirus (CAV-2) vector harboring a human GUSB expression cassette (HD-RIGIE) in the MPS VII dog brain was tested. Vector genomes, ?-glu activity, GAG content, lysosome morphology and neuropathology were analyzed and quantified. Our data demonstrated that CAV-2 vectors preferentially transduced neurons and axonal retrograde transport from the injection site to efferent regions was efficient. HD-RIGIE injections, associated with mild and transient immunosuppression, corrected neuropathology in injected and noninjected structures throughout the cerebrum. These data support the clinical evaluation of HD CAV-2 vectors to treat the neurological defects associated with MPS VII and possibly other neuropathic lysosomal storage diseases. |
| Publication | Molecular Therapy: The Journal of the American Society of Gene Therapy |
| Volume | 22 |
| Issue | 4 |
| Pages | 762-773 |
| Date | Apr 2014 |
| Journal Abbr | Mol. Ther. |
| Language | eng |
| DOI | 10.1038/mt.2013.283 |
| ISSN | 1525-0024 |
| Library Catalog | PubMed |
| Extra | PMID: 24343103 PMCID: PMC3983960 |
| Tags | Animals, beta-Glucosidase, Brain, Disease Models, Animal, Dogs, Gene Expression Regulation, Enzymologic, Gene Transfer Techniques, Genetic Therapy, Glycosaminoglycans, Humans, Mice, Mucopolysaccharidosis VII, original |
| Date Added | 2018/09/26 - 15:49:57 |
| Date Modified | 2019/05/28 - 13:58:58 |
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