Project description
Non-invasive treatments to prevent aneurysm rupture
An aneurysm forms when a weakened section of a blood vessel wall bulges outward due to pressure from blood flow. Rupture of intracranial aneurysms can cause aneurysmal subarachnoid haemorrhage and stroke. Most patients go untreated since current preventive measures are invasive and risky. There is an urgent need for safe, non-invasive therapies, but limited knowledge of the underlying disease pathways has hampered progress. The ERC-funded Treat-PRYSM project aims to repurpose existing drugs targeting vascular disease mechanisms such as endothelial-to-mesenchymal transition and TGF-β signalling. By also investigating gender-specific influences, Treat-PRYSM will open new paths for preventing aneurysm rupture through innovative drug-based strategies.
Objective
Rupture of intracranial aneurysms (IA) results in aneurysmal subarachnoid hemorrhage (aSAH), an often fatal type of stroke. Invasive IA treatment to prevent aSAH is a high-risk procedure, limiting its use and leaving most IA patients untreated. Thus, there is an urgent need for non-invasive drugs preventing aSAH, but these are lacking as our understanding of the causal disease pathways is poor. The considerable female predominance in IA and aSAH suggests the existence of sex-specific regulation of these pathways. In the ERC PRYSM StG we identified candidate drugs lisinopril, amlodipine, tamsulosin, simvastatin and metformin associated with a reduced risk of aSAH. These targets have an inhibitory effect on the Transforming Growth Factor-β (TGF-β) pathway, a potent inducer of Endothelial-to-Mesenchymal transition (EndMT), a driver of vascular disease.
The Treat-PRYSM team’s main aim is to transition the research from the ERC PRYSM StG into innovation by performing the following activities:
1) Confirm and validate our 5 candidate drugs—lisinopril, amlodipine, tamsulosin, simvastatin and metformin—as effective drugs in reducing aSAH incidence, by employing the principle of drug repurposing and triangulating evidence from epidemiological and genetic data.
2) Find genetic evidence that the EndMT and TGF-β pathways are involved in IA pathogenesis, thereby identifying these pathways as potential therapeutic targets for the candidate drugs, using a large-scale genomics approach.
3) Determine whether the mode of action of the candidate drugs and EndMT/TGF-β pathways is influenced by sex.
4) Evaluate the opportunities for a clinical trial of the most promising candidate drug to assess its ability to inhibit growth of IAs, serving as a surrogate marker for rupture.
This approach will ultimately provide a non-invasive, cost-effective drug to prevent aSAH in patients with unruptured IAs and will significantly enhance our understanding of the disease's causal pathways.
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 genetics
- medical and health sciences clinical medicine angiology vascular diseases
- medical and health sciences basic medicine neurology stroke
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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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(opens in new window) ERC-2024-POC
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3584 CX Utrecht
Netherlands
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