Novel targeted intervention to prevent brain aneurysm rupture

ongoing

In the European Union, an estimated 15 million individuals harbour unruptured intracranial aneurysms (IAs), each at constant risk of rupture and subsequent subarachnoid haemorrhage (SAH). The imminent threat of IA rupture remains a significant clinical challenge, further exacerbated by the absence of safe and efficacious non-invasive treatments, mainly due to gaps in understanding the underlying mechanisms. Notably, intrasaccular clot formation is a prevalent feature of both ruptured and unruptured IAs, with activated platelets facilitating leukocyte recruitment. We hypothesize that platelets play a pivotal role in the development and rupture of IAs. We have identified a platelet receptor as a critical factor in IA rupture, based on compelling data from a preclinical mouse model. The goal of our ERC-POC project is to investigate and establish pharmacological inhibition of this platelet receptor as a groundbreaking therapeutic strategy for preventing IA rupture. To achieve this, we have designed a comprehensive, interdisciplinary approach encompassing a preclinical model and computational fluid dynamics applied to 3D aneurysm-like vessels. Our objectives are to validate the efficacy of inhibiting this platelet receptor in preventing IA rupture in mice and to thoroughly examine the impact of a receptor inhibitor on platelet function under dynamic conditions that mimic aneurysmal environments. Ultimately, our project aims to establish the clinical proof of targeting this platelet receptor with a leading compound to prevent IA rupture and significantly reduce the risk of SAH. By doing so, we aspire to alleviate the societal burden of intracranial aneurysms, offering a pioneering therapeutic framework for the management of unruptured IA.