Rapid falls in neurofilament levels have been observed following the initiation of effective treatment in both HIV neurocognitive disorder and multiple sclerosis.31,32 Consistent reduction in neurofilament levels has also recently been shown in trials of antisense oligonucleotide therapy in patients harbouring ALS-causing SOD1 mutations, providing an early suggestion that similar changes will occur with effective ALS treatment.10 Our modelling suggested that using plasma NFL in place of the ALSFRS-R in clinical trials offers increased power to detect treatment effects in smaller group sizes. The gene discussed is NEFL; the disease is multiple sclerosis.