Higher DPR levels are apparent in C9orf72 repeat expansion carriers compared to controls but show no clear relationship to clinical outcomes.59-61 There have been two early phase trials of expansion-targeting therapy in symptomatic C9orf72-related ALS and FTD that successfully lowered levels of CSF DPRs but failed to lower NfL levels.13,62 CSF DPR concentration is similar between those who are pre-symptomatic and those with clinically manifest disease.59-61 As such, there is no reason to expect that DPRs will be useful in predicting phenoconversion to clinically manifest disease. The gene discussed is NEFL; the disease is amyotrophic lateral sclerosis.