Modulation of hepcidin to treat iron deregulation: potential clinical applications

Expert Rev Hematol. 2016;9(2):169-86. doi: 10.1586/17474086.2016.1124757. Epub 2015 Dec 15.

Abstract

The secreted peptide hormone hepcidin regulates systemic and local iron homeostasis through degradation of the iron exporter ferroportin. Dysregulation of hepcidin leads to altered iron homeostasis and development of pathological disorders including hemochromatosis, and iron loading and iron restrictive anemias. Therapeutic modulation of hepcidin is a promising method to ameliorate these conditions. Several approaches have been taken to enhance or reduce the effects of hepcidin in vitro and in vivo. Based on these approaches, hepcidin modulating drugs have been developed and are undergoing clinical evaluation. In this article we review the rationale for development of these drugs, the data concerning their safety and efficacy, their therapeutic uses, and potential future prospects.

Keywords: Hepcidin; anemia of chronic disease; clinical trials; ferroportin; iron deficiency; iron overload.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Bone Morphogenetic Protein Receptors / antagonists & inhibitors
  • Bone Morphogenetic Protein Receptors / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Cation Transport Proteins / metabolism
  • Gene Expression Regulation
  • Hepcidins / agonists
  • Hepcidins / antagonists & inhibitors
  • Hepcidins / deficiency
  • Hepcidins / metabolism*
  • Homeostasis
  • Humans
  • Interleukin-6 / metabolism
  • Iron / metabolism*
  • Iron Metabolism Disorders / genetics
  • Iron Metabolism Disorders / metabolism*
  • Iron Metabolism Disorders / therapy*
  • Peptide Hormones / pharmacology
  • Peptide Hormones / therapeutic use
  • Signal Transduction / drug effects

Substances

  • Bone Morphogenetic Proteins
  • Cation Transport Proteins
  • Erfe protein, human
  • Hepcidins
  • Interleukin-6
  • Peptide Hormones
  • metal transporting protein 1
  • Iron
  • Bone Morphogenetic Protein Receptors