Drug therapy for sickle cell disease

Abstract

The hallmarks of sickle cell disease (SCD) are sickling-induced chronic haemolytic anaemia and acute painful events due to vaso-occlusion by rigid sickled cells. Repeated vaso-occlusive events may eventually lead to organ damage or death among patients with SCD. Several interrelated factors that may trigger sickling-dependent vaso-occlusion in SCD include infection, fever, dehydration, the density of red blood cells (RBCs), anomalies of the RBC membrane, blood viscosity and endothelial cell adhesion. In view of the remarkable advances in the understanding of the roles of these factors in the pathogenesis of SCD, attempts are being made to modulate these factors by targeting them with appropriate agents. To date, the most successful treatments of SCD include the pharmacological induction of fetal haemoglobin (Hb F) expression using hydroxyurea (HU) or butyrate and its derivatives. However, side effects and poor drug efficacy of some of these agents remain as an obstacle for many patients. In this review, promising agents that have been patented for possible therapeutic use in the treatment/management of SCD will be summarised. New therapeutic agents that have been patented in the last 5 years for possible treatment and management of SCD are catalogued with emphasis placed on new agents that are thought to induce Hb F synthesis or modify either sickle haemoglobin (Hb S) or intact sickle erythrocytes.

• antisickling agents
• sickle cell disease
• sickle haemoglobin (Hb S)