Ferroptosis blockade: beyond preservation to active graft therapy

Ferroptosis blockade: beyond preservation to active graft therapy. Download PDF Subjects Drug development Translational research In a recent study published in Cell, Veeckmans et al. Show that small molecule ferroptosis inhibitors can improve liver and lung graft function.

1 These results demonstrate that ferroptosis is an emerging targetable driver of ischemia–reperfusion injury (IRI) and highlight the critical role of ex vivo organ perfusion as a therapeutic window for graft repair before transplantation. Organ transplantation is limited by organ availability, compounded by significant changes in the demographics of the donor population. Marginal organs, prolonged preservation, donation after circulatory death and IRI all increase the risk of early allograft dysfunction in these sensitive donor organs.

Machine perfusion has revolutionized the field by enabling a dynamic assessment and potential resuscitation of the donor organs. Yet, most perfusion strategies are only supportive by providing oxygenation and, in the case of normothermic perfusion, some nutrients, and by monitoring of the organs to be transplanted. There is, however, a huge unrealized potential to intervene and tackle the mechanisms of IRI and potentially improve graft performance beyond what is currently achieved only with dynamic perfusion.

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