Novel potential therapeutics to modify iron metabolism and red cell synthesis in diseases associated with defective erythropoiesis
Amaliris Guerra,
Hamideh Parhiz,
Stefano Rivella
Affiliations
Amaliris Guerra
Department of Pediatrics, Division of Hematology, The Children’s Hospital of Philadelphia (CHOP), Philadelphia, PA
Hamideh Parhiz
Department of Pediatrics, Division of Hematology, The Children’s Hospital of Philadelphia (CHOP), Philadelphia, PA, USA; RNA Institute, University of Pennsylvania, Philadelphia, PA
Stefano Rivella
Department of Pediatrics, Division of Hematology, The Children’s Hospital of Philadelphia (CHOP), Philadelphia, PA, USA; Department of Pediatrics, Division of Hematology, The Children’s Hospital of Philadelphia (CHOP), Philadelphia, PA, USA; RNA Institute, University of Pennsylvania, Philadelphia, PA, USA; Cell and Molecular Biology affinity group (CAMB), University of Pennsylvania, Philadelphia, PA, USA; Raymond G. Perelman Center for Cellular and Molecular Therapeutics-CHOP; Penn Center for Musculoskeletal Disorders, CHOP, Philadelphia, PA, USA; Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA
Under normal conditions, iron metabolism is carefully regulated to sustain normal cellular functions and the production of hemoglobin in erythroid cells. Perturbation to the erythropoiesis-iron metabolism axis can result in iron imbalances and cause anemia or organ toxicity. Various congenital and acquired diseases associated with abnormal red cell production are characterized by aberrant iron absorption. Several recent studies have shown that improvements in red blood cell production also ameliorate iron metabolism and vice versa. Many therapeutics are now under development with the potential to improve a variety of hematologic diseases, from β-thalassemia and iron-refractory iron deficiency anemia to anemia of inflammation and polycythemia vera. This review summarizes selected mechanisms related to red cell production and iron metabolism and describes potential therapeutics and their current uses. We also consider the potential application of the discussed therapeutics on various diseases, alone or in combination. The vast repertoire of drugs under development offers new opportunities to improve the clinical care of patients suffering from congenital or acquired red blood cell disorders with limited or no treatment options.
