Experimental Autoimmune Encephalomyelitis (EAE) MOG Models

Vium offers the widely utilized Myelin Oligodendrocyte Glycoprotein (MOG) model of progressive non-remitting MS against which to validate the efficacy of potential therapeutic agents. Mice are immunized with either MOG peptide antigens MOG35-55 or longer MOG1-125.  Although disease course is similar with both peptides, MOG35-55 induced disease is primarily T cell mediated, whereas MOG1-125 is reported to be B cell dependent.  While the involvement of T cells in MS disease processes is well accepted, increasingly, B cells are regarded as also integral to pathogenesis of MS and a viable target for therapeutic intervention.  Thus disease induction with MOG1-125 provides a model for assessing therapeutics that target B cells as a mechanism of action.


Study Metrics

Automated disease scoring

Reliable disease activity index scoring requires highly trained technicians to accurately assess clinical symptoms.  At Vium technicians enter observed clinical symptoms online and the score is automatically determined producing a consistent score assignment.  A record of all clinical observations used to calculate the score are available real time on the Vium Experiment Console within the Vium Research Suite.

Activity-based circadian rhythms

The MOG model of MS is characterized by progressive paralysis. Activity metrics provide an additional measure against which to assess the disease state of mice.

Breathing Rate

Changes in breathing rate may be the result of disease processes or may occur following dosing of some therapeutics. Frequent assessment of breathing rates allows researchers to compare breathing rates across the course of the disease as well as focus on changes before and after disease induction as well as before and after therapeutic interventions.

Conventional Measures

  • Disease activity index (DAI) score
  • Body weights

MS Model Data

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Figure 1.  Response to treatment in MOG35-55 mouse MS model.   Graph shows difference in DAI scoring between FTY720 treated and control groups.  DAI scoring improves in the FYT720 treated group.

Figure 2.  Tracking motion in MOG35-55 mouse model.  Graph shows differences in average night time motion between FTY720 treated and untreated control groups.  Night time motion is improved in the treated group.


Study Design

The mouse MOG EAE model is conducted according to standard protocols (3-4). Female C57Bl/6J mice are immunized with either MOG35-55 or MOG1-125 in Complete Freund’s Adjuvant (0.2 μg/mouse). Control animals are induced with CFA only. On study day 0, mice are given 100 μl subcutaneous injections of MOG on the back at 2 sites. Pertussis toxin (0.2 μg/injection) is injected 4-6 hours post-induction and again 24 hours later.  Disease onset occurs between 10 and 14 days post-induction with maximum disease about 3-4 days after onset.

Treatment Regime

Randomization

Mice are enrolled on a rolling basis intro treatment groups on the day of disease onset (identified by DAI score > 1). Groups are balanced to ensure that the DAI score and day of disease onset are similar between all groups.

Dosing

Test articles are administered beginning the day after disease onset and continuing for up to 35 days.

Analysis

Treatment efficacy is analyzed by comparing:

  • Maximum disease severity (from the DAI)
  • Disease severity across disease course (from the DAI)
  • Body weight at study endpoint

Plots and statistical analysis are available on Vium Analytics Studio within the Vium Research Suite.

Positive control therapeutics

Several positive control therapeutics can be used including:

  • Dexamethasone (daily, IP or PO)
  • FTY720 (daily, PO)
  • Methylprednisolone (pulse therapy or q2d, IP)
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Figure 3. Sample MOG 35-55 induced MS study demonstrating significant improvement in DAIs following daily FTY720 dosing. Data shown are average +/- stdev.


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References

  1. Constantinescu CS, Farooqi N, O'Brien K, and Gran B (2011) Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Brit J Pharmacol. 164: 1079-1106.
  2. Lyons JA, San M, Happ MP, Cross AH. (1999) B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephaliogenic peptide. Eur J Immunol 29:3432-9.
  3. Krumbholz M, Derfuss T, Hohlfeld R, Meinl E. (2012) B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol 8:613-23.
  4. Bittner S, Afzali AM, Wiendl H, and Meuth SG. (2014) Myelin Oligodentrocyte Glycoprotein (MOG35-55) Induced Experimental Autoimmune Encephalomelitis (EAE) in C57BL/6 Mice. J Vis Exp 86:e51275.
  5. McCarthy DP, Richards MH, Miller SD. (2012) Mouse Models of Multiple Sclerosis: Experimental Autoimmune Encephalomyelitis and Theiler’s Virus-Inducing Demyelinating Disease. Methods Mol Biol. 900: 381-401.

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