Collagen-Induced Arthritis Model (CIA)

Rheumatoid arthritis (RA) is an autoimmune disease associated with chronic inflammation, primarily in the joints. RA is characterized by synovial inflammation, swelling and autoantibody production, which result in the destruction of cartilage and bone in the small joints of hands, wrists and feet. Vium offers a well-established rat collagen-induced arthritis (CIA) model against which to validate the efficacy of potential therapeutic compounds (1-2). In the rat CIA model, both B and T cells mediate joint inflammation and destruction with signature increases in the cytokines IL-1, IL-6, IL-17, and TNF-alpha which are validated targets for development for new therapeutics.


Vium Digital Metrics

Vium Arthritis IndexTM

The Arthritis Index provides an objective measure of function-related disease severity comparable to the traditional Arthritis score without requiring manual measurement and thus reducing potential variability that may result from manual measurements.  Vium can still record and report manual scores for comparison if so desired.

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Figure 1. Vium Arthritis Index tracks with conventional joint measurements.

Motion Metric

Vium's Motion metric tracks subject behaviour in the smart cage and reports the average motion.

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Figure 2. Vium's Motion Metric tracks loss of motion over time after induction in Mouse CIA model.  Loss of motion reliably tracks with arthritis score.

Conventional Metrics

Conventional metrics and pathology are also offered

  • Arthritis score
  • Ankle joint size (caliper)
  • Ankle joint histopathology
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Figure 2. Typical increase observed in arthritis score in Vium's Mouse CIA model after induction.


Study Overview

We have validated our CIA model in both Mice and Rats.  Disease onset occurs between 11 to 15 days with average day of onset occurring between study day 12 & 13. Our induction rate is > 95%.

Randomization

Mice or rats are randomized into groups using motion prior to induction and disease severity at time of onset.

Dosing

Subjects are enrolled into treatment groups following a significant Vium Arthritis Index threshold score or an arthritis score of > 1.   A standard study may dose for 14 – 28 days.

Analysis

Treatment efficacy is assessed using Vium metrics and optional conventional measures to compare disease severity between vehicle control and treated groups.   Study progress, subject videos and graphs are made available to you securely via your account on Vium's Research Suite.  Data for individual animals as well as study groups can be accessed, compared and analyzed.  

Positive control therapeutics

Several positive control therapeutics can be used including:

  • Methotrexate (daily, PO)
  • Enbrel (q3d, SC)
  • Dexamethasone (daily, PO or IP)

Learn More

Vium Technical Docs

CIA Model Study Protocol

Arthritis Index

Breathing Rate Metric

Motion Metric

CIA Model References

  1. Hegen M, Keith JC Jr, Collins M, Nickerson-Nutter CL. (2008) Utility of animal models for identification of potential thereapeutics for rheumatoid arthritis. Ann Rheum Dis. 67: 1505-15.
  2. Bevaart L, Vervoordeldonk MJ, Tak PP. (2010) Evaluation of therapeutic targets in animal models of arthritis: how does it relate to rheumatoid arthritis? Arthritis Rheum. 62: 2192-205.
  3. Benedele A. (2001) Animal models of rheumatoid arthritis. J Muscoloskelet Neuronal Interact. 1: 377-85.
  4. Trentham DE, Townes AS, Kang AH. (1977) Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 146:857-68.
  5. Courtenay JS, Dallman MJ, Dayan AD, Martin A, Mosedale B. (1980) Immunisation against heterologous type II collagen induces arthritis in mice. Nature 283: 666-8.

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