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Collagen Induced Arthritis in Monkey

发布时间 2018-03-06
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         Collagen Induced Arthritis in Monkey


         Introduction


         Rheumatoid arthritis (RA) is a systemic inflammatory disorder characterized by chronic inflammation of the synovialCollagen Induced Arthritis in Monkey membrane, which over time results in damage to the joints and leads to pain and disability. Rodent models with collagen II induced arthritis (CIA) have been extensively used in academic research and pharmaceutical industry for investigating pathogenesis RA and its treatments. However, an RA model in non-human primate (NHP) is particularly useful because of the close phylogenesis that provides the cross-reactivity to human for medical product development with most modern drug manufacturing technologies. Contrary to the successful RA modeling in rodents, NHP RA model has been reported extremely difficult because of the low and 

         inconsistent disease incidence in both Rhesus macaques and Cynomolgus macaques, the most Collagen Induced Arthritis in Monkeycommonly used NHP for medical research.To resolve this issue, scientists at PharmaLegacy experimented type II collagen induced arthritis in Cynomolgus monkeys, and successfully established a reliable NHP arthritis model that can be used in rheumatology studies, as well as inflammation related anemia or pain studies, etc.


         PharmaLegacy Models and Research Tools



         Pharmacology Model

         CIA NHP Model:

         *Bovine type II collagen induced arthritis in Cynomolgus monkey

         Model Characteristics:

         

         *Disease moderate-to-severe, similar to human RA;

         *Poly-arthritis, persistent joint swelling, joint destruction and bone resorption;

         *Synovial membrane hyperplasia, inflammatory cell infiltration;

         *Pannus formation and cartilage damage



         Primary Endpoints for Evaluating Arthritis:

         *Disease incidence;

         *Arthritic incidence of proximal interphalangeal joints;

         *Measurement of joint swelling;

         *Arthritic score;

         *Animal body weight



         Available Endpoints for Monitoring Immune Response and Disease Progression: 

         *Hematology analysis;

         *Serum biomarkers (C-reactive protein, alkaline phosphatase, albumin, etc.);

         *Monkey anti-type II collagen IgG ELISA;

         *Antigen-specific T cell and B cell responses;

         *Cytokines

         Additional Endpoints for Assessing Bone Histopathology and Histomorphometry:

         *Radiology of arthritic joints and radiological image scoring (joint destruction, bone resorption and abnormal growth,              lose of articular cavity);

         *Qualitative histopathology;

         *Quantitative  histomorphometry (OsteoMeasure software system)

         *Immunohistochemistry

         
Case Study - Modeling Human Rheumatoid Arthritis in Cynomolgus 



         Bovine type II collagen induced arthritis is established in Cynomolgus monkeys with an overall ~87% of disease incidence, which is significantly higher than that in the previous reports. The average arthritic score is reduced by 55% with the treatment of reference drugs comparing with the vehicle treated group.

Collagen Induced Arthritis in Monkey

Collagen Induced Arthritis in Monkey


Representative X-ray graphs of monkey joints and Toluidine blue staining of joint sections:

                         Normal                                               CIA                                       Distal Interphalangeal Joint

   Paw     Collagen Induced Arthritis in Monkey             Collagen Induced Arthritis in Monkey        Collagen Induced Arthritis in Monkey

   Wrist  Collagen Induced Arthritis in Monkey             Collagen Induced Arthritis in Monkey        Collagen Induced Arthritis in Monkey

Complete loss of articular structure and significant numbers of infiltrated cells in CIA monkey joint.

Collagen Induced Arthritis in Monkey


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