Hepcidin agonists as therapeutic tools

Blood

Volumn 131, Issue 16, 2018, Pages 1790-1794

  Casu, Carla ^a   Nemeth, Elizabeta ^b   Rivella, Stefano ^a  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEMATOLOGIC AGENT; HEPCIDIN; HEPCIDIN AGONIST; UNCLASSIFIED DRUG; HAMP PROTEIN, HUMAN; IRON;

BETA THALASSEMIA; HUMAN; IRON HOMEOSTASIS; IRON METABOLISM; IRON OVERLOAD; KLEBSIELLA PNEUMONIAE INFECTION; NONHUMAN; POLYCYTHEMIA VERA; PRIORITY JOURNAL; REVIEW; THALASSEMIA MAJOR; VIBRIO VULNIFICUS INFECTION; YERSINIOSIS; AGONISTS; ANIMAL; HEMOCHROMATOSIS; METABOLISM; PATHOLOGY;

ANIMALS; BETA-THALASSEMIA; HEMOCHROMATOSIS; HEPCIDINS; HUMANS; IRON; POLYCYTHEMIA VERA;

EID: 85047606847     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2017-11-737411     Document Type: Review

References (61)

1. Oikonomidou PR, Casu C, Rivella S. New strategies to target iron metabolism for the treatment of beta thalassemia. Ann N Y Acad Sci. 2016;1368(1):162-168.
2. Arezes J, Nemeth E. Hepcidin and iron disorders: new biology and clinical approaches. Int J Lab Hematol. 2015; 37(suppl 1):92-98.
3. Papanikolaou G, Pantopoulos K. Iron metabolism and toxicity. Toxicol Appl Pharmacol. 2005;202(2):199-211.
4. Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001;276(11):7806-7810.
5. Rechavi G, Rivella S. Regulation of iron absorption in hemoglobinopathies. Curr Mol Med. 2008;8(7):646-662.
6. Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochim Biophys Acta. 2012; 1823(9):1434-1443.
7. Muckenthaler MU, Rivella S, Hentze MW, Galy B. A red carpet for iron metabolism. Cell. 2017;168(3):344-361.
8. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704): 2090-2093.
9. Kim A, Nemeth E. New insights into iron regulation and erythropoiesis. Curr Opin Hematol. 2015;22(3):199-205.
10. Ganz T, Nemeth E. Iron homeostasis in host defence and inflammation. Nat Rev Immunol. 2015;15(8):500-510.
11. Wang CY, Babitt JL. Hepcidin regulation in the anemia of inflammation. Curr Opin Hematol. 2016;23(3):189-197.
12. Michels KR, Zhang Z, Bettina AM, et al. Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia. JCI Insight. 2017;2(6): e92002.
13. Arezes J, Jung G, Gabayan V, et al. Hepcidin-induced hypoferremia is a critical host defense mechanism against the siderophilic bacterium Vibrio vulnificus. Cell Host Microbe. 2015; 17(1):47-57.
14. Stefanova D, Raychev A, Arezes J, et al. Endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron. Blood. 2017; 130(3):245-257.
15. Nicolas G, Chauvet C, Viatte L, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110(7): 1037-1044.
16. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113(9):1271-1276.
17. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood. 2006; 108(12):3730-3735.
18. Oikonomidou PR, Rivella S. What can we learn from ineffective erythropoiesis in thalassemia? Blood Rev. 2017;S0268-960X(17)30131-5.
19. Ginzburg Y, Rivella S. b-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. Blood. 2011;118(16):4321-4330.
20. Camaschella C, Nai A. Ineffective erythropoiesis and regulation of iron status in iron loading anaemias. Br J Haematol. 2016; 172(4):512-523.
21. Sebastiani G, Wilkinson N, Pantopoulos K. Pharmacological targeting of the hepcidin/ ferroportin axis. Front Pharmacol. 2016;7:160.
22. Powell LW, Seckington RC, Deugnier Y. Haemochromatosis. Lancet. 2016;388(10045): 706-716.
23. Gardenghi S, Marongiu MF, Ramos P, et al. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. Blood. 2007; 109(11):5027-5035.
24. Papanikolaou G, Tzilianos M, Christakis JI, et al. Hepcidin in iron overload disorders. Blood. 2005;105(10):4103-4105.
25. Weizer-Stern O, Adamsky K, Amariglio N, et al. Downregulation of hepcidin and haemojuvelin expression in the hepatocyte
26. cell-line HepG2 induced by thalassaemic sera. Br J Haematol. 2006;135(1):129-138.
27. Weizer-Stern O, Adamsky K, Amariglio N, et al. mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models. Am J Hematol. 2006;81(7):479-483.
28. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet. 2014;46(7):678-684.
29. Sonnweber T, Nachbaur D, Schroll A, et al. Hypoxia induced downregulation of hepcidin is mediated by platelet derived growth factor BB. Gut. 2014;63(12):1951-1959.
30. Schrier SL. Pathophysiology of thalassemia. Curr Opin Hematol. 2002;9(2):123-126.
31. Rivella S. b-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies. Haematologica. 2015;100(4):418-430.
32. Melchiori L, Gardenghi S, Rivella S. beta-Thalassemia: HiJAKing ineffective erythropoiesis and iron overload. Adv Hematol. 2010; 2010:938640.
33. Nicolas G, Viatte L, Lou DQ, et al. Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. Nat Genet. 2003;34(1):97-101.
34. Gardenghi S, Ramos P, Marongiu MF, et al. Hepcidin as a therapeutic tool to limit iron overload and improve anemia in b-thalassemic mice. J Clin Invest. 2010;120(12): 4466-4477.
35. Finberg KE, Whittlesey RL, Andrews NC. Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice. Blood. 2011;117(17):4590-4599.
36. Nai A, Pagani A, Mandelli G, et al. Deletion of TMPRSS6 attenuates the phenotype in a mouse model of b-thalassemia. Blood. 2012; 119(21):5021-5029.
37. Schmidt PJ, Fleming MD. Modulation of hepcidin as therapy for primary and secondary iron overload disorders: preclinical models and approaches. Hematol Oncol Clin North Am. 2014;28(2):387-401.
38. Crielaard BJ, Lammers T, Rivella S. Targeting iron metabolism in drug discovery and delivery. Nat Rev Drug Discov. 2017;16(6): 400-423.
39. Preza GC, Ruchala P, Pinon R, et al. Minihepcidins are rationally designed small peptides that mimic hepcidin activity in mice and may be useful for the treatment of iron overload. J Clin Invest. 2011;121(12): 4880-4888.
40. Ramos E, Ruchala P, Goodnough JB, et al. Minihepcidins prevent iron overload in a hepcidin-deficient mouse model of severe hemochromatosis. Blood. 2012;120(18): 3829-3836.
41. Casu C, Oikonomidou PR, Chen H, et al. Minihepcidin peptides as disease modifiers in mice affected by b-thalassemia and polycythemia vera. Blood. 2016;128(2):265-276.
42. Vadillo M, Corbella X, Pac V, Fernandez-Viladrich P, Pujol R. Multiple liver abscesses due to Yersinia enterocolitica discloses primary hemochromatosis: three cases reports and review. Clin Infect Dis. 1994;18(6): 938-941.
43. Khan FA, Fisher MA, Khakoo RA. Association of hemochromatosis with infectious diseases: expanding spectrum. Int J Infect Dis. 2007; 11(6):482-487.
44. Horseman MA, Surani S. A comprehensive review of Vibrio vulnificus: an important cause of severe sepsis and skin and soft-tissue infection. Int J Infect Dis. 2011;15(3):e157-e166.
45. Brissot P, Ropert M, Le Lan C, Loréal O. Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta. 2012;1820(3):403-410.
46. La Jolla Pharmaceutical Company. LJPC-401. http://lajollapharmaceutical.com/productpipeline/ljpc-401/. Accessed 14 February 2018.
47. Bourne G, Zhao L, Bhandari A, et al. Hepcidin mimetic PTG–300 for treatment of ineffective erythropoiesis and iron overload. In: Seventh Congress of the International BioIron Society (IBIS) Biennial World Meeting (BioIron 2017) May 7-11, 2017 [abstract]. Am J Hematol. 2017;92(8):E223.
48. Manolova V, Flace A, Altermatt P, Sundström H, Nyffenegger N, Duerrenberger F. Ferroportin inhibitors improve ineffective erythropoiesis and prevent iron loading in a beta-thalassemia disease model. In: Seventh Congress of the International BioIron Society (IBIS) Biennial World Meeting (BioIron 2017) May 7-11, 2017 [abstract]. Am J Hematol. 2017;92(8):E224.
49. Guo S, Casu C, Gardenghi S, et al. Reducing TMPRSS6 ameliorates hemochromatosis and b-thalassemia in mice. J Clin Invest. 2013; 123(4):1531-1541.
50. Schmidt PJ, Toudjarska I, Sendamarai AK, et al. An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine b-thalassemia intermedia. Blood. 2013;121(7):1200-1208.
51. Schmidt PJ, Racie T, Westerman M, Fitzgerald K, Butler JS, Fleming MD. Combination therapy with a Tmprss6 RNAi-therapeutic and the oral iron chelator deferiprone additively diminishes secondary iron overload in a mouse model of b-thalassemia intermedia. Am J Hematol. 2015;90(4):310-313.
52. Casu C, Aghajan M, Oikonomidou PR, Guo S, Monia BP, Rivella S. Combination of Tmprss6-ASO and the iron chelator deferiprone improves erythropoiesis and reduces iron overload in a mouse model of beta-thalassemia intermedia. Haematologica. 2016;101(1):e8-e11.
53. Origa R, Galanello R, Ganz T, et al. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica. 2007;92(5): 583-588.
54. Pasricha SR, Frazer DM, Bowden DK, Anderson GJ. Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with b-thalassemia major: a longitudinal study. Blood. 2013;122(1):124-133.
55. Silver RT, Gjoni S. The hematocrit value in polycythemia vera: caveat utilitor. Leuk Lymphoma. 2015;56(5):1540-1541.
56. Breda L, Rivella S. Modulators of erythropoiesis: emerging therapies for hemoglobinopathies and disorders of red cell production. Hematol Oncol Clin North Am. 2014;28(2):375-386.
57. Suragani RN, Cawley SM, Li R, et al. Modified activin receptor IIB ligand trap mitigates ineffective erythropoiesis and disease complications in murine b-thalassemia. Blood. 2014;123(25):3864-3872.
58. Dussiot M, Maciel TT, Fricot A, et al. An activin receptor IIA ligand trap corrects ineffective erythropoiesis in b-thalassemia. Nat Med. 2014;20(4):398-407.
59. Protagonist Therapeutics. Protagonist Therapeutics announces final phase 1 study results with novel hepcidin mimetic, PTG-300. https:// www.prnewswire.com/news-releases/ protagonist-therapeutics-announces-final-phase-1-study-results-with-novel-hepcidin-mimetic-ptg-300-300571268.html. Accessed 14 February 2018.
60. Ionis Pharmaceuticals. Pipeline. http://www.ionispharma.com/pipeline/. Accessed 14 February 2018.
61. Vifor Pharma. Vifor Pharma ferroportin inhibitor enters phase-I clinical trial. http://www.viforpharma.com/en/media/press-releases/ 201802/2167159. Accessed 14 February 2018.