Partners come from 10 European countries to achieve two main objectives: A) The further exploration of 3 animal models (the OBX rat, GS rat and NOD mouse) characterized by an activated immune response system (IRS), an abnormal tryptophan catabolism and a depressive-like behaviour to study the pathogenesis of inflammation-related mood disorders and the efficacy/working mechanism of anti-inflammatory and tryptophan metabolism restoring drugs. B) The in-parallel study of mood disorder patients to validate two sets of already developed biomarker tests to identify patients and individuals at risk for a mood disorder and characterized by an activated IRS to be able to treat these patients/individuals with drugs counteracting the consequences of the activated IRS/disturbed catabolism of tryptophan. Five strategic approaches (broken down in 12 workpackages) are used: 1) Study of the animal models for depressive-like behavior and aberrancies in monocytes/ macrophages, the tryptophan metabolism and the microglia-astrocyte-neuron interaction. 2/3) The validation of a high-throughput biomarker mRNA blood monocyte signature test and a biomarker test to detect an abnormal tryptophan catabolism. 4) Correlation studies between the outcomes of these biomarker tests in patients to various clinical variables, a.o. gene polymorphisms and the brain scan. 5) The therapeutic targetting of the activated IRS/abnormal tryptophan catabolism using a PDE4 inhibitor, a COX-2 inhibitor and a KMO-inhibitor in the animal models and in a phase II intervention study in depressed patients. Novel approaches are the prospective assessment of patients/individuals to identify whether changes in the IRS have any prognostic value and that the program aims at a personalized treatment of patients on the basis of their activated IRS. We heavily rely in this on the study of the animal models, which allow us to test anti-inflammatory therapeutics and to know their mechanism of action at the brain.
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Funding SchemeCP-IP - Large-scale integrating project
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