Project description
A novel therapy for rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by inflammation of the joints, leading to pain, swelling, and potential joint damage. Despite available treatments, a substantial number of patients do not achieve adequate response, highlighting the need for precision medicine and new therapeutic strategies. With the support of the Marie Skłodowska-Curie Actions programme, the DDRAsTic project aims to investigate the role of the enzyme MTHFD2 in abnormal immune responses in RA. This enzyme is implicated in the metabolism of folate and the DNA damage response in activated T cells. Preliminary data indicate that MTHFD2 is activated in RA patients. This study aims to develop novel inhibitors to mitigate hyperactive T cell responses in patients.
Objective
Rheumatoid arthritis (RA) is an autoimmune disease that affects millions of people worldwide, and its negative health burden is accelerating in the ageing population. Despite many available treatments, up to 40% of RA patients do not respond sufficiently to current therapies and the needs for a precision medicine approach and new treatments are pressing. The complexity of RA and unselective mechanisms of action of existing drugs are challenges. Current treatments also have unintended adverse effects because they affect healthy cell types in the body. The proposed project “DDRAsTic” focuses on a particular enzyme called MTHFD2, which plays a crucial role in the metabolism of folate and DNA damage response of activated T cells. Recent research and preliminary data, suggest that MTHFD2 is overactive in RA patients. DDRAsTic aims to address the hyperactive T-cell responses at the core of RA by targeting MTHFD2 with novel inhibitors that spare essential components, thereby minimizing the risk of toxicity and adverse effects. In parallel, DDRAsTic seeks to understand the underlying reasons for the limited efficacy of current RA treatments and explore potential biomarkers that can predict how patients will respond to standard therapies, with a specific focus on understanding the involvement of MTHFD2. The aim is to introduce a precision medicine approach in RA and identify a novel treatment. To achieve this, DDRAsTic adopts a multidisciplinary approach and uses patient-derived specimens, RA animal models and bioinformatics analysis from large cohorts of RA patients to undergo advanced imaging, cellular and molecular techniques. Overall, these analyses aim to provide insights into MTHFD2's regulatory role in abnormal immune responses and advance RA treatment by introducing precision medicine approaches and overcoming treatment toxicity.
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
171 77 STOCKHOLM
Sweden
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.