Translational research activities: progress basic target and clinical insights into diagnostic assays, validated targets, lead compounds and medical device interventions

This WP aims to identify diagnostic and therapeutic approaches which address the onset of cardiometabolic diseases linked to circadian disorders. The strategy is to combine literature findings, exclusive expertise held by the consortium and the insight gained from the ‘omics’-focused WP’s to create a translational program wherein molecular targets are identified and then subjected to professional drug discovery processes spanning lead identification up to the development of prospective diagnostic biomarkers. Complementing the molecular approaches, medical device based light therapy intervention protocols will be defined as part of support for WP2.

Objective 1. Develop diagnostic assays for 3 biomarker/analytes indicative of susceptibility to and/or progression of cardio-metabolic disease state related to circadian disorders. Assays will be at a standard compatible with clinical trial stratification applications and amenable for subsequent development as prospective diagnostic marker.

Objective 2. Screen two “Precedented” and two “Novel” targets identified in WP1-3 against a library of lead-like compounds and validate hits in secondary, selectivity and liability assays.

Objective 3. Validate target mechanism and hit compound efficacies in animal cardio-metabolic disease models, for example Rev-erbKO and RORKO mouse models available in Lille (WP4 output). Pre-clinical models of obesity and insulin resistance and atherosclerosis are also available in Lille.

Objective 4. Specify and supply light therapy instrumentation and regimens to support therapeutic intervention in WP2 and 3.