Efficacy of a novel anti-IL-1B receptor modulator in reducing preterm birth impact on neurovascular health

Preterm neonates ill-adapted to the extra uterine environment are prone to increased inflammation in multiple organs and the proinflammatory interleukine IL-1b has been closely implicated in brain injury associated with preterm birth (PTB). One major adverse neuronal outcome for PTB survivors is the greater propensity to develop ischemic brain lesions long after birth. Here, we hypothesize that the neural vasculature of premature infants becomes maladapted to appropriately respond to hypoxic-ischemic stress. Our project will study the molecular mechanisms underlying brain revascularisation potential in a mouse model of PTB combining in utero inflammation and neonatal metabolic stress. Our experimental design will evaluate the efficacy of newly discovered selective anti-IL-1 receptor modulator (Rytvela, Rytvel Biotech) in preserving brain vascular function; in contrast to commercially available antagonists of IL-1, Rytvela exhibits pharmacologic selectivity by inhibiting the coupled Rho kinase-MAPK pathways while desirably preserving the NF-kB pathway necessary for immunovigilance and cytoprotection. Inhibition of neonatal inflammation by targeting IL-1b signalling could thus protect children from enhanced vulnerability to brain damage and its devastating consequences on health.

Gael Cagnone
Faculty Supervisor: 
Jean-Sebastien Joyal
Project Year: