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Abstract : The discovery of therapeutics is largely a matter of information and data integration. Knowing the potential targets of a molecule and their functions is far from synonymous with knowing which physiological mechanisms need to be manipulated and how to achieve a given therapeutic effect. Indeed, the success of a therapeutic approach largely arises from the coherent manipulation of a physiological system as a whole and not from that of a target in a molecular context. As a result, holistic approaches (systems biology/medicine) become unavoidable. However, the utilisation of these processes imposes a very significant shift in analytical approaches to a given medical problem. Here, indirect approaches are much more fruitful than directly addressing the problem as it is perceived. In other words, searching under the street lamp because that is where there is light may be much less helpful than expected.

This point will be illustrated by showing how the construction of a model, validated in vivo, describing the mechanisms behind the pathogenesis and clinical progression of a poorly understood and invariably fatal neurodegenerative disorder (Creutzfeldt-Jakob Disease) directly led to the discovery of mechanisms governing long distance neuronal synchronisation, together with the means whereby they could be manipulated to considerably improve the treatment of non-degenerative psychiatric disorders. One of the most effective drugs used to this effect has long been on the market for a totally different indication (immunology) and is highly effective at 1/50th of its approved dosage. These discoveries led to a therapeutics class patent (WO/2010/29131 A1) currently being exploited.

However, this example is far from isolated. The same indirect, systems-based approach, has already led to the discovery of key mechanisms associated with oncogenesis, epithelial-mesenchyme transition (EMT), metastasis, therapeutic resistance, the rapid and effective control of multi-resistant pathogens, etc...

Biographie : Dr. François Iris, a former collaborator of Prof J. Dausset (Nobel Prize for Medicine, 1980), is the founder of Bio-Modeling Systems, a SME specialised in systems biology serving the industry (Pharma, Cosmetics, Foods, Fine Chemicals, etc.) and academic/fundamental research (collaborative projects), where he directs the integrative biology teams. He is a member of expert panels for the BMBF-funding initiative “Medical Systems Biology”, German Federal Ministry of Research, Berlin and the EC’s Directorate General for Research, Brussels, and a member of Centrale-Santé's Directorship Committee, Paris. He obtained a B.Sc (1st Class Hons) in comparative physiology and a Ph.D in zoology (genetics, physiology & biochemistry) at the University of Canterbury, New Zealand. He was awarded an MRC post-doctoral Fellowship and became an MRC Overseas Fellow (1989). He is the author/co-author of 7 international patents. Currently, Dr. Iris’ research focuses mainly on the construction of predictive models addressing CNS diseases (neurodegenerative and psychiatric disorders) and skin homeostasis.