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The Inflammasome: a novel therapeutic target for the treatment of Hypoxic Brain Injury in Neonates

Project description

A novel therapy against hypoxic brain injury in patients

Hypoxic ischaemic encephalopathy (HIE) is a brain injury that occurs when the newborn brain does not receive enough oxygen. HIE is associated with high mortality or permanent neurological disorders, including cerebral palsy and epilepsy. The scope of the EU-funded OxyBaby project is to investigate the potential of targeting the inflammasome as a treatment strategy to revert hypoxic brain injury. Using preclinical models of the condition and advanced imaging techniques, scientists will assess the efficacy of various inhibitors on neuroinflammation. Results will serve as the basis for advancing current clinical care strategies for infant patients with HIE.

Objective

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.

Coordinator

ROYAL COLLEGE OF SURGEONS IN IRELAND
Net EU contribution
€ 184 590,72
Address
ST STEPHEN'S GREEN 123
2 Dublin
Ireland

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Region
Ireland Northern and Western Border
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 184 590,72