Carbon monoxide and sickle cell disease

Sickle cell disease (SCD) is an inherited recessive hemoglobinopathy that leads to hemolytic anemia, resulting from a point mutation in the beta-globin chain of hemoglobin (Hb) (glutamic acid 6-valine) with recurrent painful episodes, significantly shortened life expectancy, and poor quality of life. As compared with the currently licensed therapeutics, the gasotransmitter carbon monoxide (CO) imparts significant protective effects via multiple physiological mechanisms demonstrated in four mouse models of SCD and also in two published clinical studies. The majority of reports of CO administration in both animal and human studies used either iCO or drug products that contain a non-CO active pharmaceutical ingredient (API) that releases CO, specifically intravenous PEG-COHb, as the mode of treatment. There has been a great deal of insight into how CO modulates SCD. There are six mechanisms that have been identified, all with substantial data to support the hypotheses. There are several key mechanisms of action supported with substantial data.