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New treatments and novel diagnostic tests for neonatal seizures based on purinergic signaling.

Project description

Finding targets to combat neonatal seizures

The neonatal period, from birth to 28 days, is the most vulnerable time in life for developing seizures. Neonatal seizures are challenging to diagnose and treat, and the stakes are high. Seizures can signify serious damage to the developing immature brain. Furthermore, ample evidence suggests that seizures can cause brain damage or exacerbate existing problems that we are still ill-prepared to respond to. NeoPur has identified a receptor with anti-convulsant properties in neonates. Elucidating its signalling pathway should help pinpoint biomarkers of seizures for more accurate diagnoses and faster responses as well as provide potential therapeutic targets for improved seizure control.

Objective

Newborns are predisposed to an increased risk of developing seizures following brain injury higher than in any other moment in a person’s life. Data from experimental models and patients suggest seizures in neonates may cause increased mortality and a higher risk of adverse neurological outcomes including cerebral palsy, developmental delay and intellectual disability. Consequently, the long-term health costs associated with seizures and neonatal brain damage are very high. To date, both diagnosis and treatment of neonatal seizures remain a clinical challenge with seizure misdiagnosis estimated to be as high as 50% and only every second patient responding to current therapies. The ATP-gated P2X7 receptor, a gatekeeper of inflammation, has recently emerged as a promising target for seizure control, showing anticonvulsant and disease-modifying properties in animals. New data produced by the supervisor now also suggest a role for P2X7 during seizures in neonates. However, to bring P2X7 further towards a clinical application, we need evidence of seizure-induced release of ATP in the brain, we must determine what are the clinical outcomes of a genetic and pharmacological targeting of P2X7 during neonatal seizures and we must identify biomarkers to better identify patients suffering from seizures. NeoPur brings together a team of experts in purinergic signalling, industrial partners developing novel P2X7 antagonists and diagnostic devices and clinicians specialised in neonates. This highly interdisciplinary and intersectoral approach will add a significant contribution to the understanding of purinergic signalling during neonatal seizures providing novel diagnostic and therapeutic approaches. The skills acquired during the research project, the excellent training record of the supervisor and host institution and the outstanding resources for learning and development available at RCSI will give me the tools necessary to become a highly employable neuroscientist.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF-EF-ST - Standard EF

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Call for proposal

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

ROYAL COLLEGE OF SURGEONS IN IRELAND
Net EU contribution
€ 184 590,72
Address
ST STEPHEN GREER 123
D02 YN77 DUBLIN 2
Ireland
Region
Ireland Eastern and Midland Dublin
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 184 590,72