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RA VI Translation into Individual Patient Care

Summary

Chronic inflammatory diseases that differ in the primary phenotype may share common genetic risk factors and also common inflammatory pathways and, consequently, targeted (biologic) therapies are effective across several indications. In the 1st FP the applicants have created an interdisciplinary clinical research environment in which large cohorts were established for molecular etiology and clinical intervention trials. Through additional professorships by the cluster but also university recruitment (e.g. atopic eczema; COPD/asthma) the scope could be substantially broadened. While RA I addresses the relationship between genomes and phenotypes on a molecular epidemiologic level in large cohorts, this RA will utilize individual in-depth genetic and genomic analysis for individual translation to patient care. Hypothesis generation in single cases will be extended to case series either followed by proof-of-concept therapeutic interventions or will give rise to cohort studies in RA I. Targeted anti-inflammatory therapies (e.g. biologics) will be examined across different indications (including patients with extreme therapy responses, e.g. in refractoriness) in a human systems biology based investigation of regulatory disease networks. A particular goal of this RA is the prototypic definition of drug efficacy on the molecular level. Targeted interventions will be used to define patients subpopulations based on long-term outcomes. The CCIMs established in the 1st FP of the cluster (now as CL XIII) and the epidemiology cluster laboratory (CL XI) will be the important interaction partners in particular with their interests to define early disease at the “point of no return”.

Contribution to the Scientific Discourse

The RA drives systematic clinical research in chronic inflammatory diseases and aims at a molecular re-definition of inflammatory disease entities, the definition of early disease as an entry point for causative therapy and investigates therapeutic response in inflammatory barrier diseases. The projects interact closely with all other RAs and will investigate (1) molecular signatures of different targeted interventions (e.g. anti-IL6, anti-TNF) in responders and non-responders, (2) algorithms to use individual full (or partial) genome analysis and other genomic/proteomic biomarkers for clinical decision in individual cases, (3) novel study designs for clinical trials using individual treatment and molecular definition of inflammatory disease entities and (4) ethical and legal implications of personalized (“genomized”) medical conduct.

Figure: Depicts Research Agenda of Research Area VI

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