title: Investigational selectin-targeted therapy of sickle cell disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Nigeria, College of Medicine, Department of Haematology/Immunology , Enugu Campus , Nigeria iheanyi.okpala@unn.edu.ng.
authors.forename: Iheanyi
authors.initials: I
authors.lastname: Okpala
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002986:Clinical Trials as Topic; D015195:Drug Design; D004730:Endothelium, Vascular / Q000378:metabolism; D006017:Glycolipids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006493:Heparin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy; D019087:Selectins / Q000187:drug effects* / Q000378:metabolism
chemical_list: D006017:Glycolipids; D019087:Selectins; C553182:rivipansel; D006493:Heparin
keywords: multimodal therapy; selectin; sickle cell disease; targeted therapy