The Disease
Inflammatory Bowel Disease (IBD) can be Crohn’s disease or ulcerative colitis – two serious, chronic diseases directly affecting the digestive system causing intestinal tissue to become inflamed, form sores, and bleed easily. The incidence of IBD is rising in developing countries around the world and approximately 5 million people worldwide are currently affected by a form of IBD.
This chronic condition is without a medical cure and commonly requires a lifetime of care. With the advent of monoclonal antibodies for use in IBD there has been a breakthrough in disease management while many more biologics are in the pipeline. Currently the global market is estimated at $16 billion and this is set to continue to rise.
Our Preclinical Testing Tools
Biomedcode offers services of preclinical drug efficacy evaluation of therapeutics using spontaneous and induced mouse models of inflammatory bowel disease (IBD) and TNBS colitis.
Mouse TNF driven Crohn's like pathology (TNF ΔARE/+)
Mouse mutant with defective post transcriptional regulation of endogenous TNF. Deregulated TNF expression leads to the gradual development of spontaneous inflammatory polyarthritis and inflammatory bowel disease with the first symptoms being detectable histologically as early as 3 weeks of age.
TNF ΔΑRE+/- model crossed to hTNFR1KI mice yields TNF ΔARE/hTNFR1KI, a dual disease model with humanized TNFR1, that offers the opportunity to test anti-hTNFR1 biologics efficacy in direct comparison to Etanercept, that blocks mouse TNF and efficaciously treats TNF ΔΑRE pathologies .
Human TNF dependent TNBS colitis
Local administration of an ethanol solution containing 2,4,6-trinitrobenzene sulfonic acid (TNBS), induces severe colonic damage, characterized by areas of necrosis surrounded by areas of acute inflammation, a pathology closely resembling human Crohn’s disease. TNBS colitis is a widely accepted model for Human Inflammatory Bowel Disease.
Read-Out Parameters
Body weight change
Histopathological evaluation of ileum or colon sections
Ex vivo colon tissue culture and local cytokine levels measurement
Platform validation
TNFΔARE/+ mice are treated and monitored from 4 weeks of age for 10-12 weeks.
TNBS induced colitis is an induced protocol including daily monitoring for the 5 days of its duration.
Competitive Advantage
TNFΔARE/+ mice reliably model human Crohn’s pathology and offer a unique combination of co-manifested pathologies including arthritis, IBD and heart valve pathology that share common aetiopathogenic mechanisms.
TNBS colitis in hTNF transgenic mice offer a unique model of colitis pathology with significant TNF involvement.
