Erythrocyte-active agents and treatment of sickle cell disease
Abstract
The sickle hemoglobin (HbS)-containing erythrocyte and its membrane represent a logical target for sickle cell disease therapy. Several antisickling agents which interfere with HbS polymerization have been studied over the last 30 years, but none has overcome the challenge of delivering high concentrations inside the sickle red blood cell without toxicity. The sickle erythrocyte membrane has also been targeted for therapeutic developments. Prevention of sickle cell dehydration by use of specific blockers of ion transport pathways mediating potassium loss from the sickle erythrocyte has been shown to be a feasible strategy in vitro, in vivo in transgenic sickle mice, and in patients. Other approaches have focused on improving the hemorheology of sickle erythrocytes and reducing their abnormal adhesion to endothelial cells. These potential treatments could be used alone or in combination with other approved therapies, such as hydroxyurea.
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