title: New strategies to target iron metabolism for the treatment of beta thalassemia.
abstract: Iron is one of the most abundant elements in the Earth and a fundamental component of enzymes and other proteins that participate in a wide range of biological processes. As the human body has no mechanisms to eliminate the excess of iron, its metabolism needs to be tightly controlled in order to avoid all the sequelae associated with high iron levels. Iron overload is the main cause of morbidity and mortality in beta thalassemia. The master regulator of iron homeostasis, hepcidin, is chronically repressed in this disorder, leading to increased intestinal iron absorption and consequent iron overload. Many groups have focused on obtaining a better understanding of the pathways involved in iron regulation. New molecules have recently been synthesized and used in animal models of dysregulated iron metabolism, demonstrating their ability to target and reduce iron load. Antisense oligonucleotides, as well as lipid nanoparticle-formulated small interfering RNAs and minihepcidins peptides, are novel agents that have already proved to be efficient in modulating iron metabolism in mouse models and are therefore promising candidates for the treatment of patients affected by iron disorders.
authors.affiliation: Department of Pediatrics, Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Paraskevi Rea
authors.initials: PR
authors.lastname: Oikonomidou
authors.affiliation: Department of Pediatrics, Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Carla
authors.initials: C
authors.lastname: Casu
authors.affiliation: Department of Pediatrics, Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
mesh_terms: D000818:Animals; D004920:Erythropoiesis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism / Q000628:therapy; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000008:administration & dosage; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000378:metabolism* / Q000628:therapy*
chemical_list: D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D007501:Iron
keywords: beta thalassemia; iron metabolism; iron overload; red blood cells