title: 2015 Clinical trials update in sickle cell anemia.
abstract: Polymerization of HbS and cell sickling are the prime pathophysiological events in sickle cell disease (SCD). Over the last 30 years, a substantial understanding at the molecular level has been acquired on how a single amino acid change in the structure of the beta chain of hemoglobin leads to the explosive growth of the HbS polymer and the associated changes in red cell morphology. O2 tension and intracellular HbS concentration are the primary molecular drivers of this process, and are obvious targets for developing new therapies. However, polymerization and sickling are driving a complex network of associated cellular changes inside and outside of the erythrocyte, which become essential components of the inflammatory vasculopathy and result in a large range of potential acute and chronic organ damages. In these areas, a multitude of new targets for therapeutic developments have emerged, with several ongoing or planned new therapeutic interventions. This review outlines the key points of SCD pathophysiology as they relate to the development of new therapies, both at the pre-clinical and clinical levels.
authors.affiliation: Pediatric Hematology/Oncology Dana-Farber/Children's Hospital Blood Disorders and Cancer Center, Boston, Massachusetts.
authors.forename: Natasha
authors.initials: N
authors.lastname: Archer
authors.affiliation: Centre De Référence Des Syndromes Drépanocytaires Majeurs, Hôpital Henri-Mondor, APHP, UPEC, Creteil, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Galacteros
authors.affiliation: Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School Boston, Massachusetts.
authors.forename: Carlo
authors.initials: C
authors.lastname: Brugnara
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D002986:Clinical Trials as Topic; D004913:Erythrocytes, Abnormal / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006801:Humans; D010100:Oxygen / Q000378:metabolism; D014652:Vascular Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000628:therapy
chemical_list: D006451:Hemoglobin, Sickle; D010100:Oxygen