Animal Models for Therapeutic Strategies

The use of animal models in development of novel therapeutic strategies is the main emphasis of this report. Creation of new animal models is an important part of this research. Discussed in this publication:

• Case studies of the use of established animal models in developing novel therapeutic strategies
• Emerging animal models for use in drug discovery and the development of new therapeutic strategies
• Development of animal models that are more predictive of drug efficacy
• Technological developments in progress
• Use of computer models and translational biomarkers to move more effectively from preclinical animal studies to the clinic
• Thought-leader interviews and a user survey are also included

Chapters 2, 3, 4, and 6 focus on the nematode Caenorhabditis elegans, the fruit fly Drosophila, the zebrafish, and the mouse, respectively. Each chapter includes cases studies of the use of each of these established animal models in developing novel therapeutic strategies for human disease. Chapters 5 and 7 focus on emerging animal models, the African clawed toad Xenopus tropicalis and emerging mammalian animal models. Each of these chapters focuses on technological developments in progress to develop tractable animal models based on these organisms. Chapter 7 also includes a discussion of the rat as an animal model, which is “reemerging” as the result of new technologies and collaborations.

Chapter 8 discusses the use of computer models and translational biomarkers in helping researchers move more effectively from preclinical animal studies to human clinical trials. Pharmaceutical and biotechnology company researchers have been increasingly applying pharmacokinetic/pharmacodynamic modeling to all stages of drug development. These models, as well as biophysical models such as those developed by Novartis and physiological models such as those developed by Entelos, can help researchers more effectively use animal model data in the design of clinical trials. In particular, they can help researchers reduce drug attrition in clinical trials due to suboptimal dosing.

Chapter 6, which focuses on the mouse, concludes with a discussion of the issue of developing more predictive animal models of drug efficacy, specifically more predictive mammalian models. One main reason for researchers’ difficulties in producing predictive mouse models is major unknown factors in disease biology. Although these factors make developing predictive animal models difficult, researchers can use animal models to learn about unknown or poorly understood areas of disease biology. This is expected to lead to the development of improved animal models as well as the development of new therapeutic strategies and drugs.

Developing animal models that are more predictive of efficacy is an iterative process. But progress is being made, as researchers apply new knowledge and experimental approaches in elucidating the biology of particular diseases to creation of animal models.