Technotes

Technotes

Collagen Induced Arthritis Monkey Model

Introduction


Rheumatoid arthritis (RA) is a systemic inflammatory disorder characterized by chronic inflammation of the synovial membrane, which over time results in damage to the joints and leads to pain and disability. It occurs in approximately 1% of adults, and approximately 2.5 times more women than men are affected. Rodent models with collagen II induced arthritis (CIA) have been extensively used in academic research and pharmaceutical industry for investigating rheumatoid arthritis (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 commonly used NHP for medicinal 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

 

 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



 Primary Endpoints for Evaluating Arthritis:

*          Disease incidence;

*          Arthritic incidence of proximal interphalangeal         joints;

*          Measurement of joint swelling;

*          Arthritic score;

*          Animal body weight


Case Study - Modeling Human Rheumatoid Arthritis in Cynomolgus Monkeys


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




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