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Pushing Boundaries in Pre-clinical Aortopathy Research

Project description

New treatment thoracic aortic aneurysms

Thoracic aortic aneurysms (TAAs) are a serious health concern, often leading to life-threatening complications like dissection or rupture. Current surgery helps, but they come with risks, and drugs only offer temporary relief. Additionally, the way treatments work in mice does not always translate to humans, making progress slow. With this in mind, the ERC-funded BREAK-OUT project aims to address these issues by studying TAA genetics and using advanced models to develop better therapies. Moreover, it is pioneering new ways, like patient-derived ‘aorta-on-a-chip’ models, to speed up the process from lab to clinic. This promises a leap forward in translational medicine. Overall, the project aims to prevent or even reverse the progression of this deadly condition.

Objective

Thoracic aortic aneurysm (TAA) entails a high risk for aortic dissection and rupture, which is a prominent cause of death in Western countries. Prophylactic surgery significantly reduces the mortality risk, but complications are relatively common. Moreover, in severe TAA conditions aneurysms often develop at other locations afterwards, exposing patients to repeated surgeries and, thus, threats. Current drug options only modestly slow down dilatation, without preventing dissections or ruptures. Clearly, a game changer in TAA patient management would be the availability of medical therapies capable of stopping or reversing aneurysm formation. Functional characterization of the known TAA genes, especially those that are linked to syndromic TAA, in relevant cell and/or mouse models has already delivered valuable insights into the disease mechanisms, prompting pre-clinical drug testing in mice. The mechanistic picture is incomplete though, encumbering the development of additional, and especially more effective, therapies. Another prevailing issue is the inefficient and/or unsuccessful translation of pharmacological mouse results to the clinic. Few compounds make it to clinical trials due to the high costs, lengthy time frames and difficulties as to patient recruitment. Additionally, while TAA mouse models allow us to study and therapeutically target disease in an in vivo setting, efficiency of ensuing compounds might not be recapitulated in humans. Building on intriguing preliminary data and the unique availability of mutant/control Fbn1 and Ipo8 mice and human induced pluripotent stem cells, this project aims to contribute to the resolution of these issues by further unravelling and therapeutically targeting the mechanisms underlying syndromic TAA. Additionally, BREAK-OUT will provide proof-of-concept that patient-derived aorta-on-a-chip models can be used for pre-clinical TAA research.

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Programme(s)

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-STG

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Host institution

UNIVERSITEIT ANTWERPEN
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.

€ 1 494 848,00
Address
PRINSSTRAAT 13
2000 Antwerpen
Belgium

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Region
Vlaams Gewest Prov. Antwerpen Arr. Antwerpen
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 494 848,00

Beneficiaries (1)

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