Scientists have discovered a new way to treat ALS and frontotemporal dementia (FTD) caused by a mutation in the C9ORF72 gene, the most common genetic cause of these two neurodegenerative diseases[1]. The problem is caused by proteins called dipeptide repeats (DPRs), which are formed from expanded GGGGCC repeats in the C9ORF72 gene[1]. Scientists developed a simple mutation – changing a single nucleotide (CUG to CCG) – that stopped the production of these toxic proteins while maintaining the presence of repetitive RNAs[1][2]. In mouse models with this mutation, behavior improved, pathological changes including motor neuron loss, inflammatory processes, and protein accumulation disappeared, although repetitive RNAs still accumulated in cells[1][2]. The same mutation also improved cell survival and phenotypes in neurons derived from patient stem cells[2]. These findings suggest that toxic DPR proteins, not repetitive RNAs, are the main problem in C9ORF72-associated ALS and FTD[1]. The results open up a new therapeutic approach aimed at blocking the production of DPR proteins instead of trying to remove repetitive RNA[2].