Abstract Details

To assess the correlation of neurofilament light chain (NfL; potential biomarker for multiple sclerosis [MS] disease activity) in the cerebrospinal fluid (CSF)/plasma in an experimental autoimmune encephalomyelitis (EAE) mouse model.

Twenty-five independent mouse EAE studies were conducted over 2 years under similar protocols (C57BL/6J mice; induction via ratMOG28-152 in complete Freund’s adjuvant). These studies aimed at assessing the effects of pharmacological interventions vs vehicle controls on changes in clinical scores and cNfL/pNfL levels. All available data were pooled and subject to meta-analysis.

In healthy mice, mean (SD) cNfL and pNfL levels were 10.4 (0.1) (n=45) and 0.42 (0.03) (n=50) ng/mL, respectively (CSF/plasma ratio ~25). In vehicle-treated EAE mice, cNfL and pNfL levels significantly increased post disease induction (pDI). At the peak of disease, cNfL and pNfL reached maximal mean (SD) values of 287 (27) (n=114) and 8.0 (0.8) (n=126) ng/mL, respectively (CSF/plasma ratio ~35). These levels remained elevated up to 1 month pDI (n=61 and n=50, respectively) and showed a ~10-fold reduction at 2 months pDI (n=10 and n=9, respectively). Overall, this meta-analysis demonstrated that correlations between pNfL vs cNfL levels and cNfL or pNfL levels vs EAE clinical scores were highly significant (p<0.0001 for all), confirming pNfL as a robust predictor of cNfL in the EAE model.

This meta-analysis suggests that the translational value of mouse EAE studies for assessing new disease-modifying therapy candidates could be increased by introducing cNfL and/or pNfL measurements. This analysis also establishes an additional measure to assess disease evolution and tissue damage in EAE mice.