Detection of glycine–proline repeat protein offers new biomarker in patients with C9orf72 expansion

The discovery of a G₄C₂ repeat expansion in C9orf72 as the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia prompted investigation into new therapies that target the aberrant RNA and protein molecules synthesized from the repeat. However, biomarkers that enable the efficacy of such treatments to be monitored are lacking. A new study has shown that the glycine–proline (poly(GP)) peptides translated from the repeats can be detected in the cerebrospinal fluid of individuals with the expansion, both before and after symptom onset. Researchers administered antisense oligonucleotides (ASOs) that target and reduce the levels of G₄C₂ RNA to cells from patients with the expansion and to a mouse model of C9orf72 ALS. The ASO treatment was associated with decreased intracellular and extracellular levels of poly(GP) proteins. The results indicate that poly(GP) levels could be used as a biomarker to assess the efficacy of therapies in patients with C9orf72 ALS.