Pharmacological intervention studies using mouse models of the inflammatory bowel diseases: Translating preclinical data into new drug therapies

Iurii Koboziev, Fridrik Karlsson, Songlin Zhang, Matthew B. Grisham

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations

Abstract

Most therapeutic agents used in clinical practice today were originally developed and tested in animal models so that drug toxicity and safety, dose-responses, and efficacy could be determined. Retrospective analyses of preclinical intervention studies using animal models of different diseases demonstrate that only a small percentage of the interventions reporting promising effects translate to clinical efficacy. The failure to translate therapeutic efficacy from bench to bedside may be due, in part, to shortcomings in the design of the clinical studies; however, it is becoming clear that much of the problem resides within the preclinical studies. One potential strategy for improving our ability to identify new therapeutics that may have a reasonable chance of success in clinical trials is to identify the most immunologically-relevant mouse models of IBD and pharmacologic strategies that most closely mimic the clinical situation. This review presents a critical evaluation of the different mouse models and pharmacological approaches that may be used in intervention studies as well as discuss emerging issues related to study design and data interpretation of preclinical studies. (Inflamm Bowel Dis 2011)

Original languageEnglish
Pages (from-to)1229-1245
Number of pages17
JournalInflammatory Bowel Diseases
Volume17
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • T-cells
  • biologics
  • blood flow
  • cell-based therapy
  • cytokines
  • regulatory T-cells
  • small molecules
  • therapeutics

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