Early diagnosis, treatment and prevention of mood disorders targeting the activated inflammatory response system
Coordinator: Hemmo DREXHAGE
Project Number: 222963
EC contribution: € 10,235,585.00
Project website: http://moodinflame.eu/
Partners come from 10 European countries to achieve two main objectives:
- 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.
- 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:
- Study of the animal models for depressive-like behavior and aberrancies in monocytes/ macrophages, the tryptophan metabolism and the microglia-astrocyte-neuron interaction.
- The validation of a high-throughput biomarker mRNA blood monocyte signature test and a biomarker test to detect an abnormal tryptophan catabolism.
- Correlation studies between the outcomes of these biomarker tests in patients to various clinical variables, a.o. gene polymorphisms and the brain scan.
- 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.