Treatment with a cell-penetrating peptide that prevented nuclear export of unprocessed C9ORF72 RNA and its subsequent translation into neurotoxic dipeptide repeat proteins reduced motor neuron damage and death both in fruit fly models of amyotrophic lateral sclerosis (ALS), and in patient-derived induced neuronal precursor cells (iNPCs). The work suggests that targeting nuclear export could be a therapeutic option in ALS, and possibly also frontotemporal dementia (FTD), where C9ORF72 mutations also play a role.

The hexanucleotide repeat expansion (HRE) GGGGCC in the noncoding region of the chromosome 9 open reading frame 72 (C9ORF72) gene is the most common cause of hereditary (40%) and apparently sporadic (5%-6%) amyotrophic lateral sclerosis (ALS).