Project description
A new treatment for pulmonary fibrosis
Pulmonary fibrosis is a fatal lung disease affecting millions worldwide. It is associated with progressive scarring and impaired breathing. Current treatments slow progression but cannot reverse damage or extend survival. A key driver of fibrosis is the accumulation of aged, dysfunctional cells, called senescent cells, that resist death and promote scarring. The ERC-funded FibroPep project targets a newly discovered interaction between two proteins, p21 and CDK4, which is essential for the survival of senescent cells and the formation of scar tissue. Specially designed synthetic peptides disrupt this interaction and selectively eliminate senescent cells in pre-clinical models. The project will now identify a lead therapeutic peptide and validate its efficacy, laying the groundwork for a potentially curative treatment.
Objective
Pulmonary fibrosis is an age-related disease characterized by progressive scarring of lung tissue, loss of respiratory function, and premature death. It is a fatal disease, affecting roughly ~5 million worldwide and causing >17.000 annual deaths in Europe alone. There is no cure for pulmonary fibrosis, as current treatments modestly slow disease progression but do not reverse fibrosis or substantially improve survival. These therapies often carry significant side effects and fail to address the underlying drivers of the disease, namely, the accumulation of senescent cells and ECM production. To meet this urgent unmet medical need, we propose a novel therapeutic strategy that selectively targets a key protein-protein interaction driving fibrosis.
We discovered that the interaction between p21 and CDK4 is critical for both the survival of senescent cells and the regulation of ECM components. Disrupting this interaction mimics the effects of p21 knockdown, which we have shown eliminates senescent cells and limits fibrosis. Based on this insight, we designed and tested synthetic peptides that bind to CDK4 and block its interaction with p21. Several of these peptides show strong binding and selective senolytic activity in vitro, demonstrating precise modulation of this novel target and offering a promising strategy for an incurable disease.
Our PoC project will advance this innovation toward therapeutic application. Specifically, we aim to identify a lead peptide with low micromolar potency and test its efficacy in a preclinical mouse model of pulmonary fibrosis, thereby reaching TRL4. This work lays the foundation for a highly specific, well-tolerated, and potentially curative treatment that addresses the root mechanisms of fibrosis rather than its symptoms alone. By targeting a previously unexplored molecular pathway, our approach offers new hope for millions affected by fibrotic lung diseases and could extend to broader applications in age-related fibrotic conditions.
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.
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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-2025-POC
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7610001 Rehovot
Israel
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