title: Modulation of hepcidin as therapy for primary and secondary iron overload disorders: preclinical models and approaches.
abstract: In this article, the authors discuss new approaches to treating iron overload diseases using hepcidin mimetics or by modulating endogenous hepcidin expression. In particular, the authors discuss lipid nanoparticle encapsulated siRNA and antisense oligonucleotide-mediated inhibition of TMPRSS6, an upstream regulator of hepcidin, and treatment with transferrin or hepcidin mimetics, including the recently described minihepcidins. In each case, in animal models of β-thalassemia, not only do the interventions affect iron absorption but they also act as disease-modifying agents that ameliorate the ineffective erythropoiesis.
authors.affiliation: Department of Pathology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 11, Boston, MA 02115, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Schmidt
authors.affiliation: Department of Pathology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Bader 124.1, Boston, MA 02115, USA. Electronic address: Mark.Fleming@childrens.harvard.edu.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology / Q000627:therapeutic use; D064451:Hepcidins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000188:drug therapy / Q000378:metabolism*; D014168:Transferrin / Q000494:pharmacology / Q000627:therapeutic use; D017086:beta-Thalassemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
chemical_list: D064451:Hepcidins; D014168:Transferrin; D019833:Genistein; D007501:Iron
keywords: Hepcidin/minihepcidins; Hereditary hemochromatosis; Ineffective erythropoiesis; Iron metabolism; Lipid nanoparticle siRNA/antisense oligonucleotide; β-Thalassemia