A study aiming to analyze nusinersen therapy-related changes in the cerebrospinal fluid (CSF) and serum parameters found that routine CSF markers were normal, except for blood-brain barrier dysfunction and systemic oligoclonal bands (OCBs), in adult patients with spinal muscular atrophy (SMA) type 2 or 3.

According to the authors of the study published in Clinical Drug Investigation, this could be due to repeated lumbar puncture and the immunogenic effect of nusinersen.

Nusinersen (Spinzraza)® was the first disease-modifying treatment to be approved by the US Food and Drug Administration (FDA) to treat SMA. However, robust biomarkers to assess patient response to treatment are still lacking.

Continue Reading

In the present study, a team of researchers led by Isabella Laura Simone, MD, measured routine CSF parameters, CSF markers of neurodegeneration, and serum creatinine levels in 9 patients with SMA type 2 or 3 and 10 people without a neurodegenerative disease. They then analyzed the same parameters in patients with SMA after a loading dose of nusinersen and after 4 maintenance doses. The researchers also evaluated the patients’ motor outcomes to correlate the biochemical data with motor functional status.

The results showed that there was an improvement in motor function only after the loading dose of nusinersen. There were no significant differences in routine CSF parameters or CSF markers of neurodegeneration between patients with SMA and people without a neurodegenerative disease. However, serum creatinine levels were significantly lower in patients with SMA than in the control participants. 

CSF/serum albumin ratio (Qalb) significantly increased from baseline to each time point, but there were no further increases after the maintenance doses. Qalb is one of the most reliable markers of blood-brain barrier impairment and blood-CSF barrier permeability.

OCBs were found in 5 patients and developed in 3 more patients following the loading dose of nusinersen, indicating the immunogenic effect of nusinersen. However, the researchers wrote that the presence of OCBs in serum and/or CSF at baseline should be further investigated.

Markers of neurodegeneration did not change or correlate with motor function but serum creatinine levels did. The researchers noted that biomarkers of neurodegeneration did not have a prognostic role in their group of SMA patients.


Milella G, Introna A, D’Errico E, et al. Cerebrospinal fluid and clinical profiles in adult type 2-3 spinal muscular atrophy patients treated with nusinersen: an 18-month single-centre experience. Clin Drug Investig. Published online August 13, 2021. doi:10.1007/s40261-021-01071-0