Treatment with nusinersen (Spinraza®) suppresses some neuroinflammatory factors in patients with severe spinal muscular atrophy (SMA), according to a study published in Communications Medicine.

The study found that levels of proinflammatory cytokines and neurotrophic factors were increased in the cerebrospinal fluid (CSF) of patients with SMA type 1 compared to patients with SMA type 2, type 3, and healthy controls, the researchers noted. Nusinersen reduced the levels of some, but not all, of these neuroinflammatory molecules in the patients with SMA type 1, they added.

Read more about nusinersen for SMA

Continue Reading

Proinflammatory cytokines that were found to be significantly elevated in the SMA type 1 patients before treatment with nusinersen included IL-6, IFN-γ, TNF-α, IL-2, IL-8, IL-12, IL-17, MIP-1α, MCP-1, and eotaxin. The elevated neurotrophic factors included PDGF-BB and VEGF. None of these factors were found to be significantly elevated in patients with SMA type 2 and type 3 compared to controls, the researchers noted.

After 302 days of treatment with nusinersen, patients with SMA type 1 had a significant reduction in the levels of IL-2, IL-7, IL-9, IL-12, IL-17, VEGF, eotaxin, and TNF-α. Significant differences in levels were not observed at 64 days of treatment, indicating that long-term therapy may be needed to mitigate neuroinflammation, they continued.

While changes in these molecules were not observed in less severe forms of SMA, differences in the levels of other molecules were noted during the study. Patients with SMA type 2 displayed an increase in levels of proinflammatory molecules, including G-CSF, IL-8, MCP-1, MIP-1α, and MIP-1β, while patients with SMA type 3 had a decrease in antiinflammatory IL-1ra levels following treatment with nusinersen.

“Our results reveal prominent signatures of neuroinflammation that are specifically associated with severe SMA and their partial suppression by nusinersen therapy. They also suggest that pharmacological approaches addressing the outstanding signatures of neuroinflammation in nusinersen-treated SMA patients may deserve consideration as candidate combination therapies,” the authors said.

A total of 48 pediatric patients with SMA and 4 pediatric nonneurological control subjects were included in the study. The patients with SMA included 18 patients with SMA type 1, 19 with SMA type 2, and 11 with SMA type 3.


Nuzzo T, Russo R, Errico F, et al. Nusinersen mitigates neuroinflammation in severe spinal muscular atrophy patients. Commun Med. Published online February 15, 2023. doi:10.1038/s43856-023-00256-2