Targeting RNA G‐quadruplexes as new treatment strategy for C9orf72 ALS / FTD

The recent discovery of a pathogenic expansion of a ( GGGGCC ) n repeat in the C9orf72 gene in amyotrophic lateral sclerosis ( ALS ) and frontotemporal dementia ( FTD ) led to a burst of mechanistic discoveries. In this issue, Simone et al ([Simone R, 2018]) describe novel compounds targeting the G‐quadruplex (G‐Q) structure of the ( GGGGCC ) n repeat RNA that alleviate the hallmarks of C9orf72 disease in patient‐derived neurons and increase survival in a Drosophila model. Lack of overt off‐target effects and toxicity suggest that these small molecules are promising lead compounds to the development of a therapy.