The prevalence of multiple sclerosis (MS) has been rising since 2013, and as of 2020 it was estimated to affect 2.8 million individuals globally 1. Significant progress has been made in recent decades in the understanding of MS, particularly the relapsing-remitting phase of the disease, and a number of effective disease modifying therapies (DMTs) are now available. However, many of these DMTs are associated with undesirable side effects and are ineffective in treating progressive forms of MS. Thus, there is an urgent need to develop novel therapies that are efficacious in progressive MS and exhibit an improved side effect profile.

Experimental autoimmune encephalomyelitis (EAE) is a representative animal model, which manifests, like MS, CNS-related histopathological findings, motor deficits and, inflammatory responses. EAE is one of the most successful disease models in the CNS field, and now in its 90th year 2, the neuroimmune mechanisms responsible for the phenotype have been well described 3. The immunomodulator, fingolimod, a sphingosine 1-phosphate (S1P) modulator, is the first oral drug that has been approved for treating MS and has been broadly used as a positive control in the EAE mouse model 4-7.

Fingolimod treatment prevents disease progression in EAE

Fingolimod treatment prevents disease progression in EAE
Figure 1: Clinical score – comparison of prophylactic and therapeutic dosing of fingolimod
The prophylactic group was given fingolimod from day 2 and the treatment group was given fingolimod when 50% of immunized animals had developed clinical signs of EAE. All data are presented as mean ± SEM. **p < 0.01. Naïve: n=6, EAE vehicle: n=14, EAE prophylactic: n=10, EAE treatment: n=10

Translational biomarkers: Increased plasma neurofilament light chain (NfL) in EAE is inhibited by fingolimod

Increased plasma neurofilament light chain (NfL) in EAE is inhibited by fingolimod
Figure 2: NfL quantification in plasma
NfL levels in plasma were quantified using the Mesoscale discovery platform. All data are presented as mean ± SEM. **p < 0.01. Naïve: n=6, EAE vehicle: n=13, EAE prophylactic: n=10, EAE treatment: n=10

The mechanisms of disease manifestation in EAE are well established. Therefore, the model can be broadly used for neuroimmunology programs beyond MS. Clinical score and NfL measurements can be combined with other analyses to provide a more comprehensive profiling of compound efficacy:

  • Quantification of cytokine levels in CNS, spleen, and plasma
  • Western immunoblotting to evaluate selected signalling pathways (e.g. NLRP3)
  • CNS histopathology

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