Descripción del proyecto
Biomarcadores para los resultados del tratamiento de enfermedades inmunitarias
En muchas enfermedades inmunitarias, como la enfermedad de Crohn y la artritis reumatoide, el sistema inmunitario requiere supresión. Aquí es donde entra en juego las terapias biológicas, como la administración de anticuerpos terapéuticos dirigidos contra proteínas inflamatorias o el bloqueo de la actividad/tráfico de las células inmunitarias. Sin embargo, el éxito del tratamiento es variable y no existen biomarcadores capaces de predecir la respuesta clínica, lo cual genera un sufrimiento innecesario a los pacientes y elevados costes sanitarios. El equipo del proyecto METHYLOMIC, financiado con fondos europeos, se centra en la epigenética como método para predecir el resultado de las terapias biológicas. Los investigadores introducirán y validarán biomarcadores de metilación del ADN como factores pronósticos precisos de la respuesta al tratamiento.
Objetivo
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.
Ámbito científico
- 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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Régimen de financiación
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinador
1105AZ Amsterdam
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