Sickle cell disease: current therapeutic approaches

Abstract

Sickle cell disease (SCD) is an inherited blood disorder characterised by polymerisation of deoxygenated intracellular sickle haemoglobin (HbS), leading to the deformation of red blood cells (RBC) and the assumption of various sickled shapes. These rigid sickled cells trigger a cascade of vaso-occlusive events, including local inflammation and endothelial injury, leading to painful episodes, chronic haemolytic anaemia and possible end-organ damage and premature mortality. As the first disease whose genetic aetiology was defined more than half century ago, SCD has attracted a great deal of attention from many scientists and researchers worldwide. This has led to major insights into the natural history of SCD, the pathophysiological importance of polymerisation of deoxygenated HbS, and approaches directed towards the prophylaxis or treatment of the complications associated with the disease. Despite such advances, medical management still remains suboptimal and SCD continues to be a significant cause of mortality, morbidity and health disparities worldwide. Hydroxyurea (HU), a potent inducer of fetal haemoglobin (HbF) that inhibits HbS polymerisation, is currently the only approved therapeutic agent for SCD therapy, but its long-term benefits and toxicities are controversial and are still being investigated. Over the past few decades, other novel mechanisms of SCD pathophysiology have been identified in addition to HbS polymerisation. Several of these mechanisms present appropriate targets for drug development and novel therapy for SCD. This article presents a review of potential candidate drugs that have been recently studied and patented as possible pharmacological treatment/management options for SCD.

Keywords::

• antisickling agent
• fetal haemoglobin
• sickle cell disease (SCD)
• sickle haemoglobin