Explore Validated In Vivo IBD Models

Translate your IBD therapeutics to the clinic with well-characterized in vivo models to understand the preclinical efficacy of Crohn’s disease (CD) and ulcerative colitis (UC) agents. Select well established preclinical models with diverse mechanisms capturing the distinct clinical and pathological features of IBD:

• Chemically induced IBD models, including acute and chronic dextran sodium sulfate (DSS) models resulting in UC-like disease
• Adoptive T cell transfer model for studying T cell driven UC and CD

Acute DSS IBD Model

• Evaluate innate immune system involvement in intestinal inflammation, using a model with an initial acute, predominantly Th1 immune response in the colon
• Rapidly evaluate agents in the prophylactic setting, with IBD induced in 10-14 days
• Assess agents targeting compromised mucosal barrier function, induced by DSS administration, activating neutrophils and macrophages
• Study the factors maintaining or reestablishing the integrity of the epithelium during or after injury
• Compare efficacy and response with a validated cyclosporine A (CsA) positive control

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Figure 1: Disease Activity Index: Stool consistency score + stool blood score + body weight score. Disease activity index measured in naïve vs animals administered DSS + vehicle or CsA

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Figure 2: Effects of prophylactic treatment of the calcineurin inhibitor CsA orally once daily improves colon weight:length ratio in a DSS-induced mouse model

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Figure 3: Inflammation, epithelial erosion, and submucosal edema in naïve vs. animals administered DSS + vehicle or varying levels of CsA

Chronic DSS IBD Model

• Explore increased T cell involvement compared with acute DSS induction, with mixed Th1/Th2 response with a bias towards Th1 in the colon
• Test treatments in semi-therapeutic and therapeutic settings in a chronic IBD model (study duration 30 days)
• Compare efficacy and response with a validated fingolimod (FTY-720) positive control

T Cell Adoptive Transfer Model

• Study the role of Tregs, pathogenic T cells, and other T cell populations in mucosal inflammation
• Evaluate agents targeting T cell driven UC and CD, with Th1/Th17 biased inflammation, beginning 3 weeks post transfer and peaking 5-6 weeks post-transfer
• Compare efficacy and response with a validated anti-mIL-12 antibody positive controls

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Figure 4: Effects of anti-IL-12 treatment in a T cell transfer mouse model

Streamline and Enhance Your IBD Drug Development

Benefit from an experienced scientific team to support and streamline your research with:

• Rapid study initiation to accelerate your development timelines
• Efficient on-site integration of in vivo imaging, biomarker, flow cytometry, and histology analysis
• Robust and rapid results, with detailed reports customized to individual study needs
• Custom model development, with a demonstrated history of technical skill and scientific expertise

Choose from In-Life Measurements and Key Endpoints

Typical in-life study measurements include:

• Fecal Occult Blood Test (FOBT) using Hemoccult^® Sensa^® Single Slide Rapid Diagnostic Test kits
• Stool consistency
• Body weight
• Disease activity index (DAI)

Major endpoints:

• Colon weight:length ratio and colon histology
• Spleen weight
• Intestinal permeability assay using FITC-Dextran
• Histopathological assessment
  • Mucosal epithelium integrity
  • Neutrophil infiltration of colonic tissues
  • Inflammation, necrosis/loss, erosion, hyperplasia, and edema assessment