title: Prospects for early investigational therapies for sickle cell disease.
abstract: Sickle cell disease (SCD) is a genetic disorder characterized by the production of abnormal hemoglobin that polymerizes at low oxygen concentrations, causing the erythrocyte to adopt a sickle-shaped morphology. SCD pathophysiology is extremely complex and can lead to numerous clinical complications, including painful vaso-occlusive crises (VOC), end-organ damage, and a shortened lifespan. An impressive number of investigational drugs are currently in early stages of clinical development with prospects for use either as chronic therapies to reduce VOC frequency and end-organ damage in SCD or for use at the time of VOC onset. Many of these agents have been developed using a pathophysiological-based approach to SCD, targeting one or more of the mechanisms that contribute to the disease process. It is plausible that a multi-drug approach to treating the disease will evolve in the coming years, whereby hydroxyurea (HU) (the only drug currently FDA-approved for SCD) is used in combination with drugs that amplify nitric oxide signaling and/or counteract hemolytic effects, platelet activation and inflammation.
authors: University of Campinas - UNICAMP, INCT de Sangue, School of Medical Sciences, Hematology Center , Rua Carlos Chagas 480, 13083-878, Campinas, São Paulo , Brazil +55 19 3521 8533 ; +55 19 3289 1089 ; conran@unicamp.br.
authors: Nicola
authors: N
authors: Conran
mesh_terms: D000755:Anemia, Sickle Cell / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D015195:Drug Design; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use
chemical_list: D015507:Drugs, Investigational; D006918:Hydroxyurea
keywords: early investigational drugs; pathophysiology; sickle cell disease; vaso-occlusion