Description du projet
Biomarqueurs de l’issue du traitement pour les maladies immunitaires
De nombreuses maladies à médiation immunitaire, comme la maladie de Crohn et la polyarthrite rhumatoïde, exigent la suppression du système immunitaire. C’est ici que la thérapie biologique entre en jeu, qui peut notamment prendre la forme de l’administration d’anticorps thérapeutiques ciblant les protéines inflammatoires ou bloquant l’activité/le trafic des cellules immunitaires. Cependant, l’issue position du traitement varie et il n’existe aucun biomarqueur capable de prédire la réponse clinique, ce qui engendre des souffrances inutiles pour les patients et des coûts élevés en matière de soins de santé. Le projet METHYLOMIC, financé par l’UE, se penche sur l’épigénétique en tant que moyen de prédire l’issue des thérapies biologiques. Les chercheurs présenteront et valideront les biomarqueurs de la méthylation de l’ADN en tant qu’indicateurs précis de la réponse au traitement.
Objectif
Monoclonal antibodies have become a mainstay of therapy in common immune-mediated diseases (IMID) including Crohn’s disease (CD), rheumatoid arthritis (RA), and psoriasis (PsO). Current therapeutics include antibodies (“biologicals”) targeting inflammatory proteins such as Tumor Necrosis Factor (adalimumab), leukocyte trafficking (vedolizumab), or IL-12/IL-23 (ustekinumab). At present however, it cannot be predicted which biological will be effective in an individual patient, with only <40% of patients showing primary response to any given therapeutic. Treatment failure is associated with disease complications, and increased health care costs.. Hence the overwhelming need for predictive biomarkers to guide personalised medicine in IMID is evident. No biomarker to target therapy is validated in clinical practice.
In METHYLOMIC, we build on multiple previous cohort studies in which we confirmed epigenetic biomarkers (specifically DNA methylation) as the most stringent predictor of response to biological therapy, zooming in on CD. Specifically, we discovered and validated differential DNA methylation profiles in peripheral blood as biomarkers of response/deep remission for 3 approved biologicals in CD. Through the use of machine learning algorithms, treatment response could be predicted with up to 93% accuracy for each biological for CD, and RA.
METHYLOMICS is committed to bringing personalised treatment-selection in CD and other IMID to clinical practice. We have teamed up clinical, epigenetic, and DNA diagnostics experts, patient organisations, and companies across Europe, for further validation studies, develop a marketable rapid targeted methylation assay that we than validate in a unique prospective randomised clinical trial for CD. Efficiency and cost-effectiveness is assessed in great detail and regulatory approval is guided by experts to assure delivery of the first epigenetic kit personalised treatment of CD.
Champ scientifique
- medical and health sciencesclinical medicinerheumatology
- natural sciencesbiological sciencesgeneticsDNA
- medical and health scienceshealth sciencespersonalized medicine
- medical and health sciencesbasic medicineimmunologyimmunotherapy
- natural sciencescomputer and information sciencesartificial intelligencemachine learning
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HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinateur
1105AZ Amsterdam
Pays-Bas