Fig. 1: Low dose administration of a SARM1 BEI worsens neurodegeneration during the acute inflammatory phase of EAE.

A Design of the EAE pharmacology study testing RO-7529 at 2, 10, and 50 mg/kg starting from time of immunization. Schematic was generated using Biorender. B Mean disability clinical scores of EAE mice. Green arrows indicate worsening disability with RO-7529 at 2 mg/kg during the acute inflammatory phase. C Serum NfL levels in EAE mice on days 8, 12, 16, 21, and 28 post-immunization. Serum NfL levels at day 16 (D) and day 21 (E) from the same study. F Inflammation in lumbar spinal cord at day 28 quantified as the number of inflammatory foci containing at least 20 cells per section per mouse. G Demyelination in lumbar spinal cord at day 28 quantified using a demyelination scoring system based on anti-MBP staining. H Illustrative lumbar spinal cord sections stained with: top - hematoxylin (nuclei: blue) and eosin (cytoplasm: pink), bottom - anti-MBP (brown) and hematoxylin (nuclei: blue). Magnified white matter regions from (H, E)-stained sections demonstrate inflammatory infiltrates. The anti-MBP stained section from a RO-7529 (2 mg/kg)-treated mouse depicts a demyelination score of 3. For (B–G), n = 12 animals per group; data are shown as mean ± standard error of the mean (SEM). In (D–G), dots represent individual animals. Significance is indicated by ****P < 0.0001, ***P < 0.001, **P < 0.01 and *P < 0.05, determined by two-way ANOVA and Dunnett’s post-hoc test.