Source:http://linkedlifedata.com/resource/pubmed/id/20345765
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2010-6-22
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| pubmed:abstractText |
The finding of a secretion pathway and toxicity for mutant superoxide dismutase 1 (SOD1) raised up the possibility of using immunization approaches to reduce or neutralize the burden of toxic SOD1 species in the nervous system. Here we tested a passive immunization approach based on intracerebroventricular infusion in G93A-SOD1 mice of monoclonal antibodies specific to misfolded forms of SOD1 (mSOD1). We tested two monoclonal antibodies that bind distinct epitopes in mSOD1 and that do not bind to intact wild-type (WT) SOD1. One antibody succeeded in reducing the level of mSOD1 by 23% in the spinal cord and in prolonging the lifespan of G93A-SOD1 mice in proportion to the duration of treatment. However, another monoclonal antibody binding to a different SOD1 epitope failed to confer protection indicating that not all anti-SOD1 antibodies might be suitable for immunotherapy. Interestingly, the variable Fab fragment of an anti-SOD1 antibody was sufficient to confer some protection in G93A-SOD1 mice. The partial dispensability of Fc region should offer some advantages for development of immunotherapy with antibodies of smaller molecular size and low immunogenicity. From these results, we propose that passive immunization strategies should be considered as potential avenues for treatment of familial amyotrophic lateral sclerosis caused by SOD1 mutations.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulins,
http://linkedlifedata.com/resource/pubmed/chemical/Metals,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
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| pubmed:issn |
1471-4159
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
113
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1188-99
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| pubmed:dateRevised |
2010-7-28
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| pubmed:meshHeading |
pubmed-meshheading:20345765-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:20345765-Animals,
pubmed-meshheading:20345765-Antibodies, Monoclonal,
pubmed-meshheading:20345765-Blotting, Western,
pubmed-meshheading:20345765-Disease Progression,
pubmed-meshheading:20345765-Epitopes,
pubmed-meshheading:20345765-Fluorescent Antibody Technique,
pubmed-meshheading:20345765-Immunization, Passive,
pubmed-meshheading:20345765-Immunoglobulin Fab Fragments,
pubmed-meshheading:20345765-Immunoglobulins,
pubmed-meshheading:20345765-Immunohistochemistry,
pubmed-meshheading:20345765-Immunoprecipitation,
pubmed-meshheading:20345765-Immunotherapy,
pubmed-meshheading:20345765-Injections, Intraventricular,
pubmed-meshheading:20345765-Metals,
pubmed-meshheading:20345765-Mice,
pubmed-meshheading:20345765-Mice, Inbred C57BL,
pubmed-meshheading:20345765-Mice, Transgenic,
pubmed-meshheading:20345765-Mutation,
pubmed-meshheading:20345765-Protein Folding,
pubmed-meshheading:20345765-Superoxide Dismutase
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| pubmed:year |
2010
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| pubmed:articleTitle |
Intracerebroventricular infusion of monoclonal antibody or its derived Fab fragment against misfolded forms of SOD1 mutant delays mortality in a mouse model of ALS.
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| pubmed:affiliation |
Department of Psychiatry and Neuroscience, Research Centre of CHUQ, Université Laval, Quebec, QC, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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