A new study evaluated the correlation and predictive power of several cerebrospinal fluid (CSF) biomarkers related to functional motor scores, disease activity, and clinical outcomes in patients with spinal muscular atrophy (SMA) before and during nusinersen (Spinraza®) treatment. Researchers analyzed the levels of phosphorylated heavy chain (pNf-H), light-chain neurofilaments (NfL), total tau protein (T-Tau), neurogranin, β-secretase BACE-1, and alpha-synuclein and found that pNf-H and NfL correlated with disease severity and activity.

The study also reported that T-Tau levels correlated significantly with scores on motor function tests, indicating it could be a potentially useful marker for treatment response. This finding was specific to patients with SMA type 1, however.

Despite only being statistically correlated in SMA type 1 patients, T-Tau levels were found to be elevated at baseline in most of the SMA patients. The authors hypothesized that this may reflect how extensive neuronal degeneration is in this patient set.

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The study, published in the Journal of Cellular and Molecular Medicine, was small, with only 44 patients total across SMA types 1, 2, or 3. The authors indicated “further investigations of these CSF proteins might be beneficial for paediatric SMA subtypes and treatment modalities as an indicator for clinical outcome and should be analysed in larger cohorts.”

In total, 193 CSF samples were collected from those 44 patients, of which 16 had SMA type 1, 16 had type 2, and 12 had type 3. However, 1 patient each from SMA types 1 and 2 and 2 patients from type 3 had to be excluded from statistical analysis due to missing baseline values prior to nusinersen treatment and another 7 samples had to be excluded due to contamination by blood.

Motor function assessments performed during the trial were the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) in SMA type 1 patients as well as the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) in SMA type 2 and 3 patients. Treatment with nusinersen resulted in significant improvement in CHOP INTEND scores for SMA type 1 patients but only a significant improvement between baseline and day 300 of treatment in the RULM scores for type 2 and 3 patients.


Johannsen J, Weiss D, Daubmann A, Schmitz L, Denecke J. Evaluation of putative CSF biomarkers in paediatric spinal muscular atrophy (SMA) patients before and during treatment with nusinersen. J Cell Mol Med. Published online July 27, 2021. doi:10.1111/jcmm.16802