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From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis.

Authors: Lincecum, JM  Vieira, FG  Wang, MZ  Thompson, K  De Zutter, GS  Kidd, J  Moreno, A  Sanchez, R  Carrion, IJ  Levine, BA  Al-Nakhala, BM  Sullivan, SM  Gill, A  Perrin, S 
Citation: Lincecum JM, etal., Nat Genet. 2010 May;42(5):392-9. Epub 2010 Mar 28.
Pubmed: (View Article at PubMed) PMID:20348957
DOI: Full-text: DOI:10.1038/ng.557

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Using unbiased transcript profiling in an ALS mouse model, we identified a role for the co-stimulatory pathway, a key regulator of immune responses. Furthermore, we observed that this pathway is upregulated in the blood of 56% of human patients with ALS. A therapy using a monoclonal antibody to CD40L was developed that slows weight loss, delays paralysis and extends survival in an ALS mouse model. This work demonstrates that unbiased transcript profiling can identify cellular pathways responsive to therapeutic intervention in a preclinical model of human disease.

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RGD ID: 5490547
Created: 2011-09-16
Species: All species
Last Modified: 2011-09-16
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.