MD Biosciences performs efficacy studies for proof-of-concept as well as assays for early screening and profiling of drug candidates targeted for arthritis therapies. If there is a model or assay that you don't see listed, please contact a representative to discuss a custom assay design.
Collagen-Induced Arthritis (CIA)
The Collagen-Induced Arthritis (CIA) model is a commonly used model as it shares immunological and pathological similarities to human Rheumatoid Arthritis (RA). Arthritis is initiated by intradermal injections of Collagen Type II (CII) emulsified in Complete Freund's Adjuvant (CFA). This causes an immune response generating antibodies to CII. Therefore there is both a T cell and B cell component to the pathology. The joint destruction involves cartilage destruction, bone resporption, synovial hyperplasia and periarticular cell infiltration thereby sharing many similarities to human RA. The mCollagen Induced Arthritis model contains more neutrophils and less monocytes/macrophages than the human disease. rCollagen-Induced Arthritis has a quicker onset of disease and shorter duration than the murine model.
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Collagen Antibody-Induced Arthritis (CAIA)
The Antibody Induced Arthritis model is a rapid and synchronized alternative to the Collagen-Induced Arthritis model. A cocktail of monoclonal antibodies to CII combined with a boost of LPS is used to induce arthritis. These antibodies recognize a wide range of epitopes on the CII molecule and thereby allow formation of large immune complexes on the cartilage. Since these pre-formed antibodies are administered, the initial phase of the immune response involving T and B cell interaction is not present. This makes the model far more rapid, with onset within 48 hours of LPS boost and a total duration of as little as 10 days.
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Adjuvant-Induced Arthritis (AIA)
Complete Freund's adjuvant is used to initiate induction of arthritis. This model was the original model of RA, has been extensively used to preclinical screening of new anti-arthritis compounds and has successfully predicted activity and toxicity in multiple new therapeutics. After a single injection of the adjuvant, a rapid, reliable, robust and easily measureable polyarthritis develops. The joint pathology seen in AIA share the cartilage degradation, bone reportion and cellular influx seen in human RA. This model is also T cell and neutrophil dependant with no requirement for B cells. Cytokines of both the Th1 and Th17 phenotype (eg. IL-1, IL-6, IL-17A, IL-21) are believed to play a role in the joint pathology. As this model is generally less severe than the CIA and is transient (normally resolving after a month), lower doses of test compounds can be effective in this model. The pathology however is not limited to the extremeties as the spine, GI tract, skin and even the eyes can be affected.
CFA-Induced Monoarthritis
CFA has been widely used for the induction of RA. The injection of CFA in the tail base results in a chronic arthritis involving multiple joints, promoting a widespread systemic disease that results in severe discomfort and distress. By administering the CFA intrarticular and periarticular into the joint, you achieve a less servere monoarthritis within a few days. This disease represents many of the features of RA such as pannus formation, without complicating factors such as poor mobility, altered weight gain, systemic disease and joint ankylosis.
Pain measurements are also available with this model.
CFA-induced Arthritic Pain
Traditional methods of using mechanical, thermal or electric stimuli for assessment of pain threshold do no reflect the spontaneous behavior of subjects experiencing arthritic pain. These methods are suitable for assessment of unilateral pain in which a comparison between the response to stimuli of injured vs. the non-injured is possible. Furthermore, some of the arthritic animals have deformation of the joint, making the external tests impossible. Additionaly, no information of the leel of forepaw is available using the traditional methods. This model combines the traditional pain assessments with the Foot Print of Pain method.