Fig 1: Results of the proteomic analysis with (a) Heatmap of differentially expressed proteins between pwSMA and controls (Ctrl). The color scale on the right represents Z-score values, with yellow shades indicating increased expression levels and purple shades indicating decreased expression levels. SMA BS (Baseline) I to V represent SMA Improvers (HFMSE improvement ≥ 3 points after 6 months of nusinersen therapy), while SMA BS VI and VII represent SMA Non-Improvers (HFMSE improvement < 3 points). Each row corresponds to a protein and each column represents a sample. The visual cluster structure of the heatmap reveals differences in protein expression between individuals with SMA and controls; (b) Volcano Plot of differentially expressed proteins between pwSMA and controls (ctrl). The logarithmic change in expression levels (log2 fold change) is represented on the X-axis, while the statistical significance is shown as the negative decadic logarithm of the p-value (−log10(p-value)) on the Y-axis. Each point represents a different protein, with color-coded points indicating statistically significant differences (p < 0.05) between pwSMA and controls. Red points indicate a positive change in protein expression compared to controls, while blue points represent a negative change; (c) Results of proteomic profiling from CSF with baseline levels of CNTN5, ANTXR1, and NPTX2 in controls and SMA Improvers and Non-Improvers. Significant differences (p <0.05) are marked with an asterix (*). CNTN5 levels are decreased in SMA Improvers compared to Non-Improvers, with no significant difference compared to controls. ANTXR1 is elevated in SMA Improvers compared to Non-Improvers, again without a significant difference compared to controls. For NPTX2, no significant group differences were observed.