RNA-seq data for a small molecule alleviating C9orf72 ALS pathology by interfacing G4C2 RNA repeats with endogenous decay pathways

A hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia, or c9ALS/FTD. The RNA transcribed from the expansion, r(G4C2)exp, causes various disease-associated pathologies, including intron retention, aberrant translation that produces toxic dipeptide repeat proteins (DPRs), and sequestration of RNA-binding proteins (RBPs) within RNA foci in a subset of cells in the central nervous system. Identification of this RNA species as the central toxin in c9ALS/FTD has provided a potential therapeutic target. Here, we show a repurposed antitumor drug obtained through compound derivatization potently and selectively interacts with the disease-associated r(G4C2)exp and mitigates c9ALS/FTD disease pathologies in patient-derived spinal neurons. We performed the total RNA-seq of compound-treated cells from both ALS-patients and healthy donors to support that this small molecule has limited off targets on the human transcriptome.