Modulation of hepcidin as therapy for primary and secondary iron overload disorders: preclinical models and approaches

Hematol Oncol Clin North Am. 2014 Apr;28(2):387-401. doi: 10.1016/j.hoc.2013.11.004. Epub 2014 Jan 18.


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.

Keywords: Hepcidin/minihepcidins; Hereditary hemochromatosis; Ineffective erythropoiesis; Iron metabolism; Lipid nanoparticle siRNA/antisense oligonucleotide; β-Thalassemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Genistein / pharmacology
  • Genistein / therapeutic use
  • Hepcidins / genetics
  • Hepcidins / metabolism*
  • Humans
  • Iron / metabolism*
  • Iron Overload / drug therapy
  • Iron Overload / metabolism*
  • Transferrin / pharmacology
  • Transferrin / therapeutic use
  • beta-Thalassemia / drug therapy
  • beta-Thalassemia / genetics
  • beta-Thalassemia / metabolism*


  • Hepcidins
  • Transferrin
  • Genistein
  • Iron