Abstract
Introduction: Under conditions of blood flow, selectins mediate the intercellular adhesion between erythrocytes, leukocytes, platelets and vascular endothelium that contribute to vaso-occlusion and tissue damage in sickle cell disease (SCD). Therefore, selectin antagonists have the potential to ameliorate SCD.
Areas covered: In this review, the author discusses the cellular and molecular basis of vaso-occlusion in SCD, and presents evidence that selectin-mediated cell adhesion has clinical importance in this disorder. The author discusses molecular structure of human selectins and their physiological ligands and highlights clinical trials of selectin-targeted therapy of SCD. Herein, the author also assesses the benefits and limitations of the selectin antagonists that are currently under evaluation for SCD, and offers suggestions for the future.
Expert opinion: In Phase I and II clinical trials, rivipansel and heparin demonstrated promising efficacy and safety in SCD. Although selectin blockade could potentially impair immune response, an increased incidence of infection was not reported in SCD patients treated with heparin (n = 127) or rivipansel (n = 111). The efficacy and safety findings from Phase I and II clinical studies are encouraging the commencement of Phase III studies to further evaluate selectin-targeted therapy in SCD.
Declaration of interest
The author has no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Notes
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