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Pharmacological inhibition of macrophage activation

Project description

Inactivating little cells with big appetites could treat sepsis and rheumatoid arthritis

The immune system consists of lots of different tissues and cells, all working in concert to protect our body from threats that can harm it. Macrophages are among our protectors. These specialised white blood cells 'eat' and 'digest' cellular debris, microbes and harmful organisms, including bacteria. They are also involved in both the initiation and termination of inflammation. A macrophage-related uncontrolled inflammatory response is implicated in both sepsis and rheumatoid arthritis. The EU-funded FIREQUENCHER project is investigating a potential link between DNA damage and macrophage activation that could point to a way to put out the spreading inflammatory 'fire' using macrophage inhibitors.

Objective

Macrophages are innate immune cells that specialise in sensing and responding to the presence of pathogens and they have been causally involved in the pathogenesis of both sepsis and rheumatoid arthritis (RA). Both diseases represent a high cost to the economy and society of European countries characterized by an aging population as well as developing countries. Sepsis is the first cause of death in hospitalized patient, with an estimate of 5 million deaths each year. Currently, there are no effective treatment protocols or strategies to deal with sepsis and several approaches targeting known cellular
pathways have failed. RA is a chronic condition that affects 1% of the population worldwide. Despite the existence of established guidelines, 66% of patient inadequately respond to the therapy. Our group discovered that DNA damage is involved in the control of macrophages activation, unveiling a novel and untapped pathway potentially ripe for new approaches to modulate their activity. Thus, our proposed project is to test drugs targeting factors involved in DNA metabolism to treat inflammatory immune disease. Our plan involves a first part using an in vitro strategy to test the efficacy of the inhibitors on different macrophages cell lines and a second part involving the use of well-established animal disease models.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-POC-LS - ERC Proof of Concept Lump Sum Pilot

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Call for proposal

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(opens in new window) ERC-2019-PoC

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Host institution

IFOM-ISTITUTO FONDAZIONE DI ONCOLOGIA MOLECOLARE ETS
Net EU contribution

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.

€ 150 000,00
Address
VIA ADAMELLO 16
20139 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
Research Organisations
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Total cost

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.

No data

Beneficiaries (1)

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