Guidelines for Use of Humanized Mice in IBD Drug Discovery


     
Inflammatory Bowel Disease (IBD) is a chronic immunologically mediated disease with no known cure. Can humanized mice speed up IBD drug discovery, bringing relief to the estimated 1.4 million Americans with this difficult condition?

To support IBD research, Taconic hosted a webinar by TransCure BioServices experts: Chief Executive Officer (CEO), Dr. Patrick Nef, and Chief Scientific Officer (CSO), Dr. Sebastien Tabruyn. TransCure is a contract research organization (CRO) providing support to the pharmaceutical and biotechnology companies through preclinical candidate selection, immunosafety and efficacy in humanized mouse models related to inflammation, oncology and infectious diseases.

taconic biosciences presentation View the Webinar and Download the Presentation:

Drs. Nef and Tabruyn discussed how a CIEA NOG mouse®, engrafted with human CD34+ hematopoietic stem cells (HSCs), such as huNOG, could be used for efficacy evaluation of new IBD treatments. While multiple IBU murine models exist - chemically induced models, genetically manipulated models and bacteria-infected models - these mouse models lacks human lymphocytes and are not ideal for testing IBD drugs which target human specific immune cells or cytokines. Unlike other IBD models, this humanized mouse, huNOG, stably develops multiple human lymphocytes, which are present in peripheral blood, bone marrow, spleen, and the gut as reported here by TransCure.

In this exclusive Taconic Webinar, Drs. Nef and Tabruyn discuss in detail how a humanized NOG mouse could be an in vivo model to predict medication targeting human immune cells or cytokines for researchers who have potential IBD drugs .

"NOG mice are very versatile and multipurpose."
- Dr. Patrick Nef, CEO of TransCure

TransCure has provided the following guidelines for evaluating humanized mice for IBD research.

TransCure's Guideline for Use of huNOG in IBD Research

Study Size

  • Minimum 15 huNOG/group

IBD induction method: 40 kDa Dextran sulfate sodium (DSS) in drinking water

  • Concentration: 1-3% DSS for chronic IBD and 3-5% for Acute IBD are recommended
  • Note: DSS source and batch variability could affected severity of IBD. Each batch should be monitored and tested.

Endpoints/disease progression:

  • Survival, bleeding, weight loss, and IBD TCS scoring could be utilized.

Positive control: Mechanisms of Action (MoA) and route of administration should be considered

  • Cyclosporine-A (CSA):
    • Concentration: 10-40 mg/kg
    • Route of administration: oral administration
  • Anti-human TNF alpha:
    • Concentration: 5-20 mg/kg
    • Route of administration: Daily intraperitoneal (IP) injection
Related InsightsRelated Insights: