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Targeting IGF-1 signalling for repair of preterm brain dysmaturation

51 months
Approved budget:
Associate Professor Justin Dean
Health issue:
Obstetric complications/perinatal care
Proposal type:
Lay summary
Very premature babies continue to have extremely high rates of long-term neurodevelopmental deficits. These adverse outcomes can result from infection and inflammation around birth, and are closely associated with reduced circulating levels of a key brain growth factor, insulin-like growth factor-1 (IGF-1). We and others have shown in experimental studies that treatment with IGF-1 soon after brain injury is neuroprotective. However, immediate treatment after brain injury is seldom feasible in clinical practice, and the timing of injury is particularly unclear in preterm infants. This study will provide the first direct, head-to-head comparison of IGF-1 versus cyclic glycine-proline (a stable, bioactive, blood–brain barrier permeable IGF-1 metabolite that normalises IGF-1 bioavailability) for delayed, repair of brain injury using a clinically-relevant intranasal delivery strategy. These studies will be performed in our well-characterised newborn rodent model of very preterm inflammatory brain injury.