Total tau could become a potential biomarker for clinical improvement in patients with spinal muscular atrophy (SMA), according to a study recently published in CNS Neuroscience & Therapeutics.

“The measurement of total tau concentration in CSF is a reliable index for monitoring the biomarker and clinical response to nusinersen therapy in patients with SMA,” the authors wrote.

This longitudinal prospective, single-center study included 30 patients previously diagnosed with SMA in Croatia. Most of them (53.33%) had SMA type 1, 33.33% type 3, and only 13.33% had type 2. the majority of the participants (63.33%) were males, ranging from 1 month to 7 years of age. All patients received nusinersen, with a minimum of 5 and up to 15 doses, by the end of the study.

Continue Reading

Read more about SMA prognosis

The researchers collected cerebrospinal fluid (CSF) samples by lumbar puncture before the children received a dose of nusinersen. An enzyme-linked immunosorbent assay later determined protein concentrations, and functional motor scales assessed motor function.

The most important finding was a statistically significant negative association between nusinersen dose and total tau concentrations on the CSF. After the fourth nusinersen dose, total tau concentration decreased when compared to baseline, and showcased even lower values after the fifth, sixth, seventh, ninth, tenth, and eleventh doses. Specifically, children who had received the seventh and ninth doses had significantly lower total tau than those with only 3 doses.

These findings are of special interest since it suggests a potential use of total tau in the CSF to assess treatment efficacy and, possibly, clinical improvement. Previous attempts to identify a biomarker with this ability evaluated the concentration of S100B in the CSF. However, no relevant changes were associated with the nusinersen administration.

“Even though NfL reduction in CSF had been reported in a few studies of SMA patients on nusinersen, NfL, in general, does not seem to represent a reliable biomarker to monitor the response of SMA patients to nusinersen treatment. Finally, our study shows that t-tau concentration is emerging as a reliable,” the authors concluded.


Šimić G, Vukić V, Babić M, et al. Total tau in cerebrospinal fluid detects treatment responders among spinal muscular atrophy types 1–3 patients treated with nusinersen. CNS Neurosci Ther. Published online December 13, 2022. doi:10.1111/cns.14051