Project description
Targeting a hidden receptor to treat asthma
Asthma remains a pressing health issue, affecting 3 % of the global population and causing 1 000 deaths daily. Despite its prevalence, standard treatments for asthma have stagnated, with innovations primarily focusing on severe cases that represent only 7 % of sufferers. Consequently, 60 % of patients still face poorly controlled symptoms. This stagnation highlights a critical need for new therapeutic strategies. The ERC-funded IMMCEPTION 2 project will address this gap by targeting a novel receptor, GPCRX, implicated in asthma. Researchers have engineered a transgenic mouse model to study GPCRX, revealing its significant role in asthma pathology. IMMCEPTION 2 aims to develop a selective antagonist for GPCRX, potentially leading to a new oral treatment.
Objective
Asthma affects approximately 3% of the population and results in 1,000 daily deaths. It is characterized by chronic lung inflammation and airway hyperresponsiveness. First lines of treatment have not evolved in the last decades and actual developments are essentially focusing on severe asthma management (7% of patients) via the targeting of inflammatory mediators. Unfortunately, 60% of asthmatics still suffer from uncontrolled symptoms.
The lungs are innervated by peripheral neurons expressing specific sets of G protein-coupled receptors (GPCR) that contribute to bronchoconstriction and regulate allergic immune response. Among the broad family of GPCRs, the GPCRX has never been studied in a pathological context, albeit human and murine orthologs share a remarkable sequence identity. We have created a new transgenic mouse, GPCRXMut, allowing both to track the receptor expression and to interrogate its function in vivo. The GPCRXMut mouse exhibits normal immune and sensory systems at steady state. Our data demonstrate that a) GPCRX is expressed by both peripheral neurons and certain lung-resident immune cells; b) the selective invalidation of GPCRX completely protects against the development of asthma in various models; and c) lung biopsies from asthmatic patients show high expression of GPCRX in neurons and immune cells.
The ERC proof of concept project IMMCEPTION 2 aims to develop a selective antagonist for GPCRX to treat asthmatic patients. We will 1) miniaturize our established screening system for antagonists; 2) identify leads capable of specifically blocking GPCRX; and 3) develop a new mouse model humanized for the GPCRX to further validate identified leads in vivo.
The research program has been carefully designed to leverage our expertise in neurobiology, immunology, asthma, and clinical allergy and has the potential to lead to the development of a new oral molecule with a dual mode of action to silence lung neuroimmune circuits.
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.
- natural sciences biological sciences neurobiology
- medical and health sciences clinical medicine pneumology asthma
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine allergology
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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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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-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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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75654 PARIS
France
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