Descrizione del progetto
Una nuova terapia contro le lesioni cerebrali ipossiche nei pazienti
L’encefalopatia ipossico-ischemica (EII) è una lesione cerebrale che si verifica quando il cervello del neonato non riceve abbastanza ossigeno. L’EII è associata a un elevato tasso di mortalità o disturbi neurologici permanenti, tra cui paralisi cerebrale ed epilessia. Lo scopo del progetto OxyBaby, finanziato dall’UE, è quello di analizzare il potenziale di un intervento sull’inflammasoma e adoperarlo come strategia di trattamento per invertire gli effetti di una lesione cerebrale ipossica. Impiegando modelli preclinici della condizione e tecniche per immagini avanzate, gli scienziati avranno modo di valutare l’efficacia di vari inibitori sulla neuroinfiammazione. I risultati forniranno la base per promuovere le attuali strategie di assistenza clinica per i pazienti neonati affetti da EII.
Obiettivo
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.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinatore
2 Dublin
Irlanda