Therapeutic potential of oxygen through M101 transportation in reducing vaso-occlusion and hemolysis in a mouse model of sickle cell disease.

Abstract

Sickle cell disease (SCD) is a genetic disorder marked by hemoglobin S-induced red blood cell (RBC) sickling, causing hemolysis, vaso-occlusion, and organ damage. Despite its severity, treatment options remain limited. RBC transfusion is a highly effective therapeutic option in SCD, particularly due to its capacity to improve oxygen delivery and reduce sickling by introducing healthy red blood cells, but it is associated with a significant risk of transfusion-related complications. Our study investigates the treatment potential of M101, a novel hemoglobin-based oxygen carrier derived from the marine worm Arenicola marina, in a mouse model of SCD. M101s unique properties, including its high oxygen-carrying capacity and indirect antioxidant outcome, make it a promising candidate for ameliorating SCD pathophysiology. The study demonstrates that M101 administration significantly reduces RBC sickling and hemolysis in SCD mice. Furthermore, M101 infusion significantly prevents microvascular occlusion in liver and lung and attenuates the inflammatory response after vaso-occlusion induction. These findings highlight M101 strong potential as a novel therapeutic strategy for managing or preventing painful vaso-occlusive crises in SCD. Further research is warranted to determine the optimal dosing regimen and to evaluate the long-term safety and efficacy of M101 in humans.