Project description
Treatment outcome biomarkers for immune diseases
In many immune-mediated diseases such as Crohn’s disease and rheumatoid arthritis the immune system requires suppression. This is where biological therapy comes in, such as the administration of therapeutic antibodies targeting inflammatory proteins or blocking the activity/trafficking of immune cells. However, treatment success is variable and there are no biomarkers capable of predicting clinical response, causing unnecessary suffering to patients and high healthcare costs. The EU-funded METHYLOMIC project focuses on epigenetics as a means of predicting the outcome of biological therapies. Researchers will introduce and validate DNA methylation biomarkers as accurate predictors of response to therapy.
Objective
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.
Fields of science
- 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
Keywords
Programme(s)
Funding Scheme
HORIZON-RIA - HORIZON Research and Innovation ActionsCoordinator
1105AZ Amsterdam
Netherlands
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Participants (13)
1101 BV Amsterdam
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1930 Zaventem
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20132 Milano
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6720 Szeged
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1000 Ljubljana
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9000 Gent
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1649 028 Lisboa
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
3584 CM Utrecht
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
2645LT DELFGAUW
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
08014 Barcelona
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
1081 HV Amsterdam
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1000 Bruxelles / Brussel
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3645WG Vinkeveen
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
Partners (4)
Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
4102 Seraing
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The organization defined itself as SME (small and medium-sized enterprise) at the time the Grant Agreement was signed.
Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
94080 South San Francisco
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Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
OX1 2JD Oxford
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Partner organisations contribute to the implementation of the action, but do not sign the Grant Agreement.
WC2R 2LS London
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