From Transcriptome Analysis to Therapeutic anti-CD40L Treatment in the SOD1 Model of Amyotrophic Lateral Sclerosis

Nat Genet. 2010 May;42(5):392-9. doi: 10.1038/ng.557. Epub 2010 Mar 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / metabolism
  • Animals
  • CD40 Ligand / antagonists & inhibitors*
  • CD40 Ligand / immunology
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling
  • Humans
  • Immune System
  • Inflammation
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Signal Transduction
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1

Substances

  • SOD1 protein, human
  • CD40 Ligand
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1