This month’s Drug Discovery Today Editor’s choice deals with the topic of Animal Models. I suppose that this is a topic that doesn’t necessarily attract masses of attention; people tend to concentrate on what is exciting and new in their own particular field and, to an extent, are not so interested in the intricacies of animal modelling.
If, however, you were to look at failures of compounds in clinical trials, depending upon which reports you read, you would find that the major cause of failure at Phase II is lack of efficacy (around 50%) and only about 20% fail at this stage as a result of safety issues. So, I suppose that one must assume that failures as a result of efficacy, in the main, must come about from failures in target identification and/or validation or, alternatively, from inappropriate models of disease.
The translation of promising ideas and compounds to clinic will be improved by more effective target validation, something which is easier said than done. Improvements in animal modelling will hopefully facilitate target validation and candidate selection and enhance the quality and likely success of experimental drugs. In the first of our free highlighted articles,“Predictive in vivo animal models and translation to clinical trials”,Natalie Cook, Duncan I. Jodrelland David A. Tuveson discuss those models used to investigate cancer and the pros and cons of each system. They further outline how genetically engineered mouse models (GEMMs) have progressed and how and why their application in drug development have lagged behind.
Following on from this and moving away from cancer, where there are a relatively large number of clinically-validated targets, the second of our free downloads “Animal models of Alzheimer’s disease
and drug development” by Bart Laurijssens, Fabienne Aujard and Anisur Rahman covers quite a different field. They discuss the various models used in the development of drugs for Alzheimer’s disease. The article critically examines these models and discusses reasons why they may be ineffective in predicting efficacy in human trials.
In the final paper of this newsletter, we revisit the cancer arena in the article “Emergence of zebrafish models in oncology for validating novel anticancer drug targets and nanomaterials”. Zebrafish models have become very popular of late, as they represent a relatively high-throughput, cost-effective means of examining the effects of drugs in a living species with demonstrated similarities to various organ systems in humans. They are amenable to genetic manipulation, easy to dose and provide a halfway house between isolated cell systems and “black box” testing of compounds. As such, these models provide a system that gives information that would be difficult to achieve from other test systems and in a time frame that is compatible with modern drug discovery programmes.
Steve Carney was born in Liverpool, England and studied Biochemistry at Liverpool University, obtaining a BSc.(Hons) and then read for a PhD on the Biochemistry and Pathology of Connective Tissue Diseases in Manchester University, in the Departments of Medical Biochemistry and Histopathology, supervised by Professor DL Gardner and Dr. John Anderson. On completion of his PhD he moved to the Kennedy Institute of Rheumatology, London, where he worked with Professor Helen Muir FRS and Professor Tim Hardingham, on the biochemistry of experimental Osteoarthritis. He subsequently joined Eli Lilly and Co. and held a number of positions in Biology R&D, initially in the Connective Tissue Department, but latterly in the Neuroscience Department. He left Lilly in 2002 to take up his present position as Managing Editor, Drug Discovery Today, at Elsevier. He has authored over 40 peer-reviewed articles, written several book chapters and has held a number of patents.