A nucleotide GGGGCC-repeat expansion in the C9ORF72 gene is found in amyotrophic lateral sclerosis (ALS), but how this triggers disease is unclear. This paper used induced pluripotent stem cells (iPSCs) derived from patients with ALS as a model. These cells had enhanced glutamate excitotoxicity and altered transcription — effects that were also seen in brain samples from patients with ALS. In addition, the RNA-binding protein ADARB2 (RNA-editing deaminase B2) interacted with the GGGGCC repeat in iPSCs, showing that toxicity is due to a gain-of-function mechanism. Antisense oligonucleotides to the C9ORF72 gene reversed the phenotype of the iPSCs.
References
Donnelly, C. J. et al. RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Cell 80, 415–428 (2013)
Rights and permissions
About this article
Cite this article
Harrison, C. Patient stem cells give clues to ALS. Nat Rev Drug Discov 12, 906 (2013). https://doi.org/10.1038/nrd4187
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrd4187
