Heme Oxygenase in Sickle Cell Disease

There is substantial research supporting a therapeutic role for the heme oxygenase enzyme and its metabolite the gasotransmitter, carbon monoxide in sickle cell disease.  This enzyme and its associated gasotransmitter have been shown to reduce inflammation and vaso-occlusion in a number of transgenic sickle cell mouse studies and also in vitro research.  In addition, clinical studies have shown a reduction in sickling and increase in red blood cell survival after inhalation of carbon monoxide.  Moreover, an epidemiological study of environmental levels of this metabolite of the heme oxygenase pathway demonstrated lower hospital admissions for sickle cell crises on days with higher environmental carbon monoxide.   

There are two primary mechanism of action.  First, the heme oxygenase enzyme and certain of its metabolites, including carbon monoxide act in an anti-inflammatory and anti-apoptotic manner by down-regulating genes associated with inflammation (NFκB, VCAM-1, and ICAM-1) and increasing key anti-oxidant pathways (Nrf-2, HO-1).  Second,  carbon monoxide, binds tightly to hemoglobin to prevent the formation long rigid chains, preventing red blood cells from sickling.  Please see the Citations for more information.

The targeting of the heme oxygenase pathway in sickle cell disease could potentially provide safe and effective relief to these patients in dire medical need.