Journal
JOURNAL OF NEUROSCIENCE METHODS
Volume 201, Issue 1, Pages 228-238Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneumeth.2011.08.003
Keywords
Lentiviral vectors; Chondroitinase ABC; Corticospinal tract; Spinal cord injury; Axon regeneration
Categories
Funding
- Wellcome Trust
- Newton Trust
- European Union [223524]
- PERSIST [222878]
- Spinal Cord Repair
- Cambridge University Trinity College
- Christopher and Dana Reeve Foundation
- NIHR Cambridge Biomedical Research Centre
- Medical Research Council
- International Spinal Research Trust
- International Spinal Research Trust [TRI002/1] Funding Source: researchfish
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Several diseases and injuries of the central nervous system could potentially be treated by delivery of an enzyme, which might most effectively be achieved by gene therapy. In particular, the bacterial enzyme chondroitinase ABC is beneficial in animal models of spinal cord injury. We have adapted the chondroitinase gene so that it can direct secretion of active chondroitinase from mammalian cells, and inserted it into lentiviral vectors. When injected into adult rat brain, these vectors lead to extensive secretion of chondroitinase, both locally and from long-distance axon projections, with activity persisting for more than 4 weeks. In animals which received a simultaneous lesion of the corticospinal tract, the vector reduced axonal die-back and promoted sprouting and short-range regeneration of corticospinal axons. The same beneficial effects on damaged corticospinal axons were observed in animals which received the chondroitinase lentiviral vector directly into the vicinity of a spinal cord lesion. (C) 2011 Elsevier B.V. All rights reserved.
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