CRC TRR 128: Initiating/Effector versus Regulatory Mechanisms in Multiple Sclerosis - Progress towards Tackling the Disease

Basic data for this project

Description

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS). This CRC elucidates the complex crosstalk between the immune and the nervous system at molecular, cellular and systems biology levels, using a highly interdisciplinary and translational approach. Projects within this consortium are organized into research subclusters focusing on i) immune regulatory networks and disease initiation, ii) immune cell trafficking, iii) immune-mediated damage and repair and iv) environment. The third funding period will continue this successful organization but with the integration of novel information across i) models, ii) modalities and iii) patient cohorts, thus enhancing the strong clinical translational perspective of this CRC. Based on ambitiously fostering mechanistic insights in MS pathology, with the overall goal to improve patients' fate, a first strategic pillar is the integration of different well-curated cohorts with multidimensional clinical, imaging and biological data acquisition (analysed within the central clinical translation platform Z02). The integration of information across models (experimental), modalities (e.g., immune phenotypes, MRI phenotypes, soluble markers/signatures) and patient cohorts (including exploratory trials) allows an iterative refinement of pathogenetic and therapeutic principles applicable to MS and related neuroimmunological diseases (triangulation of evidence, forward, reverse and refined translation). A second strategic pillar is the use of cutting-edge technologies and analytic approaches (e.g., single cell approaches, high-end imaging) in different, partly under-investigated compartments (e.g., lymph nodes, meninges) to better understand the functional specialization of immune and nervous system crosstalk under steady-state, inflammatory and therapeutic conditions. A third strategic pillar is the implementation of exploratory human studies (serving hypothesis generation and/or validation). This will aid the development and validation of markers as well as therapeutic targets. Taken together, the vision for the next funding period is to contribute to the development of pathomechanistic knowledge and patient-relevant deliverables to help drive the worldwide search for prognostic and therapeutic improvement in the field of multiple sclerosis, and thus neuroimmunology.