Bioxodes presented the latest developments of its lead candidate Ir-CPI at ESOC 2023.
Valérie PireauxA, Stéphanie DemoulinA, Estelle HessA, Joël TassignonA, Sandrine DerochetteA, Hans WarrinnierA, Edmond GodfroidA
- A Bioxodes SA, Gosselies, Belgium
Title of the abstract
Ir-CPI reduces brain infiltration of neutrophils releasing extracellular traps and attenuates neuronal degeneration after intracerebral haemorrhage
Background and aims
A major contributor to poor outcomes after intracerebral haemorrhage (ICH) is secondary brain injury that notably involves neuroinflammation with early activation of microglia, release of proinflammatory mediators and infiltration of inflammatory cells including neutrophils. Experimental ICH models showed that neutrophils damage the brain by producing reactive oxygen species, releasing proinflammatory proteases and
neutrophil extracellular traps (NETs), affecting blood brain barrier permeability and worsening neuronal death.
In a murine model, we evaluated Ixodes ricinus-Contact Phase Inhibitor (Ir-CPI), an inhibitor of neutrophil-mediated thromboinflammation, on evolution of perihematomal oedema (PHO) and haemorrhage volumes, on neutrophil infiltration and neuronal degeneration.
ICH was induced by injection of bacterial collagenase into the right striatum. Mice were allocated either to PBS, Ir-CPI or enoxaparin (n = [6-8]). Treatments were administered intravenously immediately post-stroke induction as a bolus followed by a 3-day infusion.
Ir-CPI did not increase PHO and haemorrhage volumes measured by magnetic resonance imaging 1 and 3 days after ICH, as compared to PBS. Ir-CPI decreased neutrophil infiltration and significantly decreased the number of neutrophil-releasing NETs at collagenase injection site (p < 0.05). Ir-CPI also reduced the number of degenerating neurons in the haemorrhagic zone (p < 0.05 at the injection site). In contrast, enoxaparin increased oedema and haemorrhage volumes as compared to Ir-CPI (p < 0.05) and PBS and had no significant impact on neutrophil infiltration and on degenerating neurons.
Administration of Ir-CPI in mice post-ICH induction is safe, reduces neutrophil infiltration including neutrophil-releasing NETs, and attenuates neuronal degeneration.