Description du projet
Une thérapie innovante contre les lésions cérébrales hypoxiques chez les patients
L’encéphalopathie ischémique hypoxique (HIE) est une lésion cérébrale qui survient lorsque le cerveau du nouveau-né ne reçoit pas suffisamment d’oxygène. Elle est associée à des taux de mortalité élevés ou à des troubles neurologiques permanents, notamment la paralysie cérébrale et l’épilepsie. L’objectif du projet OxyBaby, financé par l’UE, est d’étudier le potentiel de ciblage de l’inflammasome, en tant que stratégie de traitement pour guérir les lésions cérébrales hypoxiques. Grâce à des modèles précliniques de la pathologie et à des techniques d’imagerie avancées, les scientifiques évalueront l’efficacité de plusieurs inhibiteurs sur la neuro-inflammation. Les résultats obtenus serviront de base pour faire avancer les stratégies de soins cliniques actuelles pour les nouveaux-nés atteints de HIE.
Objectif
Following 4.5 years abroad I hope to work as a MSCA Fellow to tackle the issue of deleterious neuroinflammation following hypoxic injury in newborns. Hypoxic Ischemic Encephalopathy (HIE) describes brain injury that occurs when an infant’s brain does not receive enough oxygen & blood. Approximately 15-25% of patients die, 1 in 4 develop severe and permanent neurological disorders including, Cerebral Palsy & later-life Epilepsy. There are currently no successful treatment options & HIE has withstood attempts to improve outcome. A critical immune complex, the inflammasome was discovered in 2002 that senses ‘danger’ & processes potent inflammatory cytokines to bioactive forms. I have generated novel data demonstrating a role for the inflammasome & specifically targeting it for treatment of hypoxic brain injury. This study advances this by assessing the exact contribution of its activity on a cellular level & temporally targeting the complex as a novel treatment. I will employ established preclinical models of hypoxic brain injury, advanced imaging techniques (2- photon) & novel small molecule inhibitors of the complex. I will work at the Royal College of Surgeons in Ireland (RCSI) with supervisor Prof David Henshall, Director of the FutureNeuro Centre, a multi-institutional national centre for chronic & rare neurological disease research. Ultimately, our proposal will aid design & improvement of current clinical care strategies for infant patients with HIE. I will work with top neuroscientists within FutureNeuro & Europe (Prof Mallard, Sweden), the leading inflammasome company, Inflazome & its CSO Prof O’ Neill and Neonatologists including Prof Murray (Cork, Ireland). My collaboration with these leaders across multiple sectors will expand my competencies/transferable skills & allow advanced multidisciplinary training from experts. All of these will combine to leave me well-placed to provide meaningful contributions to Europe’s competitiveness and growth in the future.
Champ scientifique
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
2 Dublin
Irlande