RAP-011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice

American Journal of Hematology

Volumn 90, Issue 1, 2015, Pages 8-14

  Langdon, Jacqueline M ^a   Barkataki, Sangjucta ^a   Berger, Alan E ^a   Cheadle, Chris ^a   Xue, Qian Li ^a   Sung, Victoria ^b   Roy, Cindy N ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CELGENE CORPORATION   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACE-011; ACTIVIN RECEPTOR 2; ACTIVIN RECEPTOR TYPE II-A; ACTRIIA-MIGG2AFC FUSION PROTEIN; ERYTHROPOIETIN; HAMP1 PROTEIN, MOUSE; HEMOGLOBIN; HEPCIDIN; HYBRID PROTEIN; IMMUNOGLOBULIN G; IRON; LIGAND;

ANIMAL; BLOOD; BLOOD CELL COUNT; C57BL MOUSE; CHEMISTRY; DRUG EFFECTS; ERYTHROID PRECURSOR CELL; ERYTHROPOIESIS; FEMALE; GENETICS; METABOLISM; SPLEEN; TRANSGENIC MOUSE; TRANSPORT AT THE CELLULAR LEVEL;

ACTIVIN RECEPTORS, TYPE II; ANIMALS; BIOLOGICAL TRANSPORT; BLOOD CELL COUNT; ERYTHROID PRECURSOR CELLS; ERYTHROPOIESIS; ERYTHROPOIETIN; FEMALE; HEMOGLOBINS; HEPCIDINS; IMMUNOGLOBULIN G; IRON; LIGANDS; MICE, INBRED C57BL; MICE, TRANSGENIC; RECOMBINANT FUSION PROTEINS; SPLEEN;

EID: 84919625439     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.23856     Document Type: Article

References (48)

1. Hattangadi SM, Wong P, Zhang L, et al. From stem cell to red cell: Regulation of erythropoiesis at multiple levels by multiple proteins, RNAs, and chromatin modifications. Blood 2011;118:6258-6268.
2. Koury MJ, Ponka P. New insights into erythropoiesis: The roles of folate, vitamin B12, and iron. Annu Rev Nutr 2004;24:105-131.
3. Hentze MW, Muckenthaler MU, Galy B, et al. Two to tango: Regulation of Mammalian iron metabolism. Cell 2010;142:24-38.
4. Roy CN. Anemia of inflammation. Hematology Am Soc Hematol Educ Program 2010;30:276-280.
5. Coyne DW, Kapoian T, Suki W, et al. Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: Results of the Dialysis Patients' Response to IV Iron with Elevated Ferritin (DRIVE) Study. J Am Soc Nephrol 2007;18:975-984.
6. Ganz T. Hepcidin and iron regulation, 10 years later. Blood 2011;117:4425-4433.
7. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004;306:2090-2093.
8. Donovan A, Brownlie A, Zhou Y, et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 2000;403:776-781.
9. McKie AT, Marciani P, Rolfs A, et al. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell 2000;5:299-309.
10. Roy CN, Mak HH, Akpan I, et al. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood 2007;109:4038-4044.
11. Nicolas G, Bennoun M, Porteu A, et al. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc Natl Acad Sci U S A 2002;99:4596-4601.
12. Weinstein DA, Roy CN, Fleming MD, et al. Inappropriate expression of hepcidin is associated with iron refractory anemia: Implications for the anemia of chronic disease. Blood 2002;100:3776-3781.
13. Du X, She E, Gelbart T, et al. The serine protease TMPRSS6 is required to sense iron deficiency. Science 2008;320:1088-1092.
14. Finberg KE, Heeney MM, Campagna DR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008;40:569-571.
15. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352:1011-1023.
16. Ganz T, Olbina G, Girelli D, et al. Immunoassay for human serum hepcidin. Blood 2008;112:4292-4297.
17. Costa E, Swinkels DW, Laarakkers CM, et al. Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in haemodialysis patients. Acta Haematol 2009;122:226-229.
18. 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;113:1271-1276.
19. Sasu BJ, Cooke KS, Arvedson TL, et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood 2010;115:3616-3624.
20. Steinbicker AU, Sachidanandan C, Vonner AJ, et al. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood 2011;117:4915-4923.
21. Theurl I, Schroll A, Sonnweber T, et al. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood 2011;118:4977-4984.
22. Schwoebel F, van Eijk LT, Zboralski D, et al. The effects of the anti-hepcidin Spiegelmer NOX H94 on inflammation-induced anemia in cynomolgus monkeys. Blood 2013;121:2311-2315.
23. Efficacy of NOX-H94 on Anemia of Chronic Disease in Patients With Cancer. Clinical Trials.gov identifier NCT01691040. NOXXON Pharma AG.
24. Lexaptepid Pegol (NOX-H94) in ESA-hyporesponsive Anemia in Dialysis Patients. Clinical Trials.gov identifier NCT02079896. NOXXON Pharma AG.
25. Walton KL, Makanji Y, Harrison CA. New insights into the mechanisms of activin action and inhibition. Mol Cell Endocrinol 2012;359:2-12.
26. Fields SZ, Parshad S, Anne M, et al. Activin receptor antagonists for cancer-related anemia and bone disease. Exp Opin Invest Drugs 2013;22:87-101.
27. Carrancio S, Markovics J, Wong P, et al. An activin receptor IIA ligand trap promotes erythropoiesis resulting in a rapid induction of red blood cells and haemoglobin. Br J Haematol 2014;165:870-882.
28. Ruckle J, Jacobs M, Kramer W, et al. Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 2009;24:744-752.
29. Raje N, Vallet S. Sotatercept, a soluble activin receptor type 2A IgG-Fc fusion protein for the treatment of anemia and bone loss. Current Opin Mol Ther 2010;12:586-597.
30. Sherman ML, Borgstein NG, Mook L, et al. Multiple-dose, safety, pharmacokinetic, and pharmacodynamic study of sotatercept (ActRIIA-IgG1), a novel erythropoietic agent, in healthy postmenopausal women. J Clin Pharmacol 2013;53:1121-1130.
31. Iancu-Rubin C, Mosoyan G, Wang J, et al. Stromal cell-mediated inhibition of erythropoiesis can be attenuated by Sotatercept (ACE-011), an activin receptor type II ligand trap. Exp Hematol 2013;41:155-166 e117.
32. Dussiot M, Maciel TT, Fricot A, et al. An activin receptor IIA ligand trap corrects ineffective erythropoiesis in beta-thalassemia. Nat Med 2014;20:398-407.
33. A Phase 2a Study To Evaluate The Pharmacokinetics, Safety, Efficacy, Tolerability, And Pharmacodynamics of Sotatercept (ACE-011) for the Correction of Anemia in Subjects With End-stage Renal Disease on Hemodialysis. Clinical Trials.gov identifier NCT01146574. Celgene Corporation.
34. Study of Sotatercept for the Treatment of Anemia in low-or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) or Non-proliferative Chronic Myelomonocytic Leukemia (CMML). Clinical Trials.gov identifier NCT01736683. Celgene Corporation.
35. Study to Determine the Safety and Tolerability of Sotatercept (ACE-011) in Adults With Beta(β)-Thalassemia. Clinical Trials.gov identifier NCT01571635.: Celgene Corporation.
36. Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia (ACE-011-DBA). Clinical Trials.gov identifier: NCT01464164. North Shore Long Island Jewish Health System.
37. Nutrient Requirements of Laboratory Animals. Washington, D.C.: The National Academies Press; 1995.
38. Prince OD, Langdon JM, Layman AJ, et al. Late stage erythroid precursor production is impaired in mice with chronic inflammation. Haematologica 2012;97:1648-1656.
39. Torrance J, Bothwell T. Tissue Iron Stores. New York, NY: Churchill Livingstone 1980.
40. Socolovsky M, Nam H, Fleming MD, et al. Ineffective erythropoiesis in Stat5a(-/-)5b(-/-) mice due to decreased survival of early erythroblasts. Blood 2001;98:3261-3273.
41. Chen K, Liu J, Heck S, et al. Resolving the distinct stages in erythroid differentiation based on dynamic changes in membrane protein expression during erythropoiesis. Proc Natl Acad Sci U S A 2009;106:17413-17418.
42. Lesbordes-Brion JC, Viatte L, Bennoun M, et al. Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis. Blood 2006;108:1402-1405.
43. 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;110:1037-1044.
44. Pak M, Lopez MA, Gabayan V, et al. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006;108:3730-3735.
45. Kautz L, Jung G, Valore EV, et al. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014;46:678-684.
46. Skikne BS. Serum transferrin receptor. Am J Hematol 2008;83:872-875.
47. Porpiglia E, Hidalgo D, Koulnis M, et al. Stat5 signaling specifies basal versus stress erythropoietic responses through distinct binary and graded dynamic modalities. PLoS Biol 2012;10:e1001383.
48. Lehmberg K, Grosse R, Muckenthaler MU, et al. Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients. Ann Hematol 2013;92:387-394.