"Multiple Sclerosis (MS) is a devastating disease of the central nervous system affecting 2.5 million worldwide. MS is a field of constant therapeutic innovation, a fact which brings hope to young adults since MS is one of the most frequent causes of severe handicap. A major unmet need is to rationalize treatment decisions. To date, there is no way of predicting which patients will best respond to one of the 15 drugs expected on the market by 2014 and which patients are at risk of severe adverse effects. Recent technical advances (the omics revolution) have brought the dream of personalized medicine (PM) closer to reality. Therefore the main objective of this project is to design a composite test (using genome based biomarkers associated with clinical and radiological information) in order to predict which patients are associated with the best benefit to risk ratio in MS treatment, using Natalizumab (NTZ) as the paradigm. For this purpose, we have already built up a unique cohort of 1500 Europeans MS patients with. We will address 5 secondary objectives: #1 determine a qualitative definition of response to NTZ with clinical and radiological parameters; #2 determine a quantitative biological response test based on an in vitro assay; #3 determine DNA-based biomarkers associated with NTZ response; #4 determine genetic susceptibility to progressive multifocal encephalopathy and NTZ-related severe adverse events; and #5 determine RNA-based biomarkers associated with NTZ response. When this work is completed, we will use the data generated to build our composite test with a multivariate approach. We postulate that our predictive test for choosing the best patients to treat with NTZ will be a paradigm for all MS treatment and, beyond MS, for biotherapies in general. This project should have a positive impact on patients’ quality of life and on the MS market, and will involve a network of 5 teams (4 academic and 1 SME) that will work in perfect synergy."