title: Promising therapies in sickle cell disease.
abstract: Despite the fact that sickle cell anemia was one of the first diseases to have a demonstrated genetic etiology, to date there is still only one approved therapy for this disease. Recent increases in our understanding of the pathophysiology of the disease should translate into improved and more rapid development of newer therapies. This review will focus on the following current and potential therapeutic strategies to reduce the morbidity of sickle cell anemia. 1) Therapies such as decitabine, hydroxyurea, butyrate, lenalidomide and pomalidomide, which decrease the polymerization rate of HbS by increasing the concentration of Hb F; 2) Drugs that decrease relative intracellular HbS concentration by increasing total cell volume via inhibition of normal membrane ion exchange channels, such as KCL Cotransporter and Gardos Channels. These inhibitors include magnesium pidolate, imidazole antimycotics, arginine and Senicapoc; 3) Treatment of sickle cell vasoocclusion through inhibition of endothelial or cell surface adhesion molecules, such ICAM 4 and alpha(v)beta(3) integrins, by drugs related to the GPII(b)III(a) inhibitors or adhesion molecule modulators, and 4) Attempts to achieve vasodilation by nitric oxide and antioxidant therapy. This review will discuss the status of these emerging therapies in the treatment of sickle cell anemia.
authors.affiliation: Division of Hematology, Montefiore Medical Center, 3411 Wayne Avenue, Bronx, NY 10467, USA. rraghupa@montefiore.org
authors.forename: Radha
authors.initials: R
authors.lastname: Raghupathy
authors.forename: Henny H
authors.initials: HH
authors.lastname: Billett
mesh_terms: D000755:Anemia, Sickle Cell / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006801:Humans; D014664:Vasodilation / Q000187:drug effects
chemical_list: D006451:Hemoglobin, Sickle