Drug Discovery Today: The Value of Experiments on Human Tissues

Robert A Coleman
Pharmagene Laboratories Ltd., 2 Orchard Road, Royston, Hertfordshire, SG8 5HD, UK

Review article :AATEX 10(1):24-35
Abstract
The imbalance between drug discovery and development expenditure on the one hand, and the output of new medicines on the other is giving great cause for concern. The low success rate in transitioning new drugs from clinical candidates into successful drugs results from a variety of issues, arguably, one of which is the over-reliance on the use of non-human species in the discovery/development process. There is currently a great deal of enthusiasm for the mouse as a surrogate for man, particularly since it has been shown how similar mice are to men in terms of their respective genomes. This enthusiasm has been increased by the development of the technologies through which it has become posible to manipulate the mouse genome in order to explore the functions of specific genes. However, despite the genomic sir hilarities between mouse and man, there are still clearly demonstrable phenomic differences. A study of the expression profiles of genes that encode drug targets has revealed that while some are expressed in highly similar fashion in mouse and man, for others the patterns of expression are quite different. A rational alternative to the use of experimental animals in pharma research /is to make more use of donated human tissue. Two examples of drug discovery programmes based exclusively on human tissue data are outlined: 1. the development of human secretin as a novel treatment for cystic fibrosis (CF); and 2. the development of 5-HT2B antagonists for the treatment of irritable bowel syndrome (IBS).

Key words: human tissue, drug discovery, gene expression, cystic fibrosis, IBS


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