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

Abstract

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 (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.