Project description
Innovative imaging for precision asthma therapy
Asthma is a chronic respiratory condition characterised by inflammation and narrowing of the airways, leading to symptoms like shortness of breath. A key cause is the abnormal production of thick, sticky mucus which accumulates in the airways and obstructs normal airflow. Eosinophils play a role in asthma, as they contribute to mucus stickiness and hinder its clearance. The ERC-funded CRYSTAL-SHINE project has developed crystal-dissolving antibodies that improve mucus clearance in mice. However, further clinical development is hindered by the lack of a biomarker for mucus that is rich in Charcot-Leyden crystals (CLCs). To overcome this obstacle, CRYSTAL-SHINE will develop a PET tracer for non-invasive imaging of CLCs, thereby improving the monitoring of antibody treatment.
Objective
Asthma is characterized by airway obstruction, causing difficulty in breathing. The major cause of therapy resistant obstruction is mucus plug buildup in 60% of severe asthmatics. Mucus plugs form as a result of abnormal mucus production by airway barrier cells and recruitment of eosinophils that change the mucus from a gel- to a glue-like state. Eosinophils also release galectin-10 (Gal10) protein, which crystallizes and forms Charcot-Leyden crystals (CLC). My advanced ERC grant unraveled how CLCs damage the epithelium to aggravate airway inflammation, cause more mucus build-up and physically impede the clearance of plugs, because of their needle-like shape. We therefore developed crystal-dissolving antibodies, that improve mucus clearance in mice. Meanwhile we also found that chronic rhinosinusitis (CRS) and 10% of cystic fibrosis (CF) patients have CLC-rich mucus. The current problem we are facing in the further clinical development of crystal dissolving antibodies is that we do not have a biomarker for CLC-rich mucus, and therefore it would be hard to predict which patients benefit from treatment with CLC-dissolving antibodies. The solution is to develop a non-invasive imaging technique to visualize crystal-containing mucus. We have therefore generated a Gal10 PET tracer. We have
developed humanized mice that express Gal10 and form CLCs in their airways, and will be used to test the feasibility of Gal10 PET tracer imaging. A major challenge is to find the best conjugation format of the PET
biomarker, and unravel the pharmacokinetics and - dynamics of the imaging modality. In parallel, we will test if Gal10 antibodies bind to human biopsies from asthma, CRS and CF patients, and how this biomarker correlates to CLC presence. Gaining PoC that Gal10 PET imaging works as a biomarker to detect CLCs will personalize the approach and create deal-making value for our antibody program.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences clinical medicine pneumology asthma
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmacokinetics
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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.1.1 - European Research Council (ERC)
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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.
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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-ERC-POC - HORIZON ERC Proof of Concept Grants
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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) ERC-2024-POC
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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.
9052 ZWIJNAARDE - GENT
Belgium
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