A novel drug discovery method based on systems biology: combination therapy and biomarkers for Multiple Sclerosis
Financing: Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement nº 305397
Duration: 01/01/2013 – 01/01/2015
The CombiMS consortium aims to develop a new method for drug discovery based on systems biology and to apply this method to the discovery of combination therapies for MS. This consortium brings together 8 different partners (both SMEs and academic/public research organisations) that have been selected for their expertise and capacity in their given field. The Project Coordinator is Bionure Farma (ES), which will be also in charge of analyzing the signaling pathways through phosphoproteomic assays of the blood samples from patients with MS. The other 2 SMEs involved in the project, Anaxomics (ES) and ProtAtOnce (GR), together with the European Molecular Biology Laboratory (UK) and Karolinska Institutet (SE) (public research organizations) will joint efforts and expertise in the design of computational models adopting a systems perspective to integrate the knowledge generated by ‘omics technologies and clinical data with the aim of identifying combination therapies for MS. While the academic /public research beneficiaries will provide samples and clinical info from patients with MS in order to perform the phosphoproteomic assays and will also perform molecular and cellular immunological studies to validate the models’ predictions: The Institute of Biomedical Research August Pi Sunyer (ES), University of Zurich (CH), Karolinska Institute (SE) Neuroimmunology Unit, and Charit Berlin (DE).
The therapeutic challenge of complex diseases requires the use of combination therapies to target the distinct mechanisms and pathways involved. Such complex diseases will benefit from the design of computational models adopting a systems perspective to integrate the knowledge generated by ‘omics technologies and clinical data. Multiple Sclerosis is a prototypic debilitating complex disease in which an autoimmune attack is launched against the brain. Current therapies for MS are far from effective and target only part of the immune response. Hence, the need to develop combination therapies with good safety profiles that better control this condition, the main aim of CombiMS. By understanding how current MS therapies work in biological networks and taking advantage of novel compounds, more effective combination therapies will be designed for MS. Indeed, the tools developed will be applicable to other immune and complex diseases to improve their therapeutic options in the future. The data for the modelling process will be generated from biological and clinical samples, and the predictions about combination therapies from the computational models tested using in vitro and animal models of MS. Given the limitations of animal models in translational research, we shall focus on studying the phosphoproteome in samples from individuals with MS (PBMC) using xMAP technology. The phosphoproteome has been identified as a system likely to be affected in MS and the novel therapeutic compounds that will be tested are known to act through signalling pathways involving receptor tyrosine kinases. The mechanistic modelling will be extended to the different levels of the response to therapy by analysing biological networks integrating gene and protein networks, with drugs, their effects and side-effects. As well as developing new combination therapies for MS, CombiMS will provide proof of concept of the useful short term results that a systems biology drug discovery approach can provide.