Analysis of the cerebrospinal fluid (CSF) may yield important information regarding treatment with nusinersen (Spinraza®) in patients with spinal muscular atrophy (SMA), according to an article recently published in Muscle & Nerve.

“This might reflect the medication’s effect and a possible therapeutic biochemical marker,” the authors wrote.

This prospective, observational study included 50 patients previously diagnosed with SMA, of whom the majority (44%) had type 1, followed by type 2 in 35% of the cases, and lastly, type 3 in 22%. All participants underwent consecutive CSF analyses during an ongoing treatment scheme with nusinersen administered intrathecally.

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At baseline, the average protein concentration was at normal values, and levels began to increase as treatment was initiated. At treatment administration number 9, protein values showcased an important increment.

Interestingly, only patients with SMA types 2 or 3 exhibited this pattern. Patients with SMA type 3 had protein values above baseline after the second administration, reaching their highest point at the seventh dose. Those with SMA type 2 increased their protein concentration at the second dose, then lowered below baseline at the third, and finally ended at the highest value among all 3 types at the ninth administration.

On the other hand, the protein concentration in the CSF of patients with SMA type 1 even dropped from baseline at the fourth dose, maintaining such levels until the eighth dose, reaching baseline values, and finally increasing slightly at the ninth dose.

“The observation that nusinersen affects the protein concentration is consistent with the medication mechanism for altering the splicing of the SMN2 gene mRNA, thus increasing the concentration of the functional SMN protein,” the authors explained.

Nusinersen is an oligonucleotide that alters the pre-messenger RNA (pre-mRNA) of the SMN2 gene, promoting the survival of the cells in the anterior horn. Its administration is intrathecally, previously removing a predetermined quantity of CSF. Hence, identifying potential disease markers in the CSF would yield an important advantage in the management of these patients.


Orbach R, Sagi L, Sadot E, et al. Cerebrospinal fluid characteristics of patients treated with intrathecal Nusinersen for spinal muscular atrophy. Muscle & Nerve. Published online October 10, 2022. doi:10.1002/mus.27731