Oral Carbon Monoxide Therapy In Murine Models Of Sickle Cell Disease: Beneficial Effects On Vaso-Occlusion, Inflammation And Anemia

Carbon monoxide (CO) at low, non-toxic concentrations has recently emerged as a powerful biological response modifier that exerts anti-inflammatory protection in many animal models of tissue inflammation and injury including sickle cell disease (SCD). The protection observed was associated with modulation of the innate and adaptive immune response and restoration of tissue and organ function. CO may also have a role as an antipolymerization hemoglobin S agent. Inhaled CO gas has been used to generate the majority of preclinical and clinical data regarding CO. However, inhaled CO is challenging to precisely dose given the variability of patient ventilation. Furthermore inhaled CO has environmental safety concerns for patients, as it requires the presence of large amounts of compressed CO gas in cylinders. Oral administration of CO avoids many of the issues associated with gas administration and provides a platform for outpatient administration. An oral formulation that would deliver low, non-toxic concentrations of CO, might be a better alternative for treating SCD patients.