Anti-repulsive Guidance Molecule C (RGMc) Antibodies Increases Serum Iron in Rats and Cynomolgus Monkeys by Hepcidin Downregulation

AAPS Journal

Volumn 17, Issue 4, 2015, Pages 930-938

  Böser, Preethne ^a,b   Seemann, Dietmar ^a   Liguori, Michael J ^a   Fan, Leimin ^a   Huang, Lili ^a   Hafner, Mathias ^b   Popp, Andreas ^a   Mueller, Bernhard K ^a  

^a ABBVIE INC   (United States)

^b UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

ABT 207; h5F9 AM8; hepcidin; PK PD analysis; safety assessment

Indexed keywords

ABT 207; H5F9 AM8; HEMOJUVELIN; HEPCIDIN; IRON; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG; MEMBRANE PROTEIN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; DOWN REGULATION; DRUG MECHANISM; DRUG SAFETY; FEMALE; HISTOPATHOLOGY; IC50; IRON BINDING CAPACITY; IRON BLOOD LEVEL; LIQUID CHROMATOGRAPHY; MACACA FASCICULARIS; MASS SPECTROMETRY; NONHUMAN; POLYMERASE CHAIN REACTION; PROTEIN EXPRESSION; RAT; SINGLE DRUG DOSE; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; COMPARATIVE STUDY; DRUG EFFECTS; GENETICS; MALE; SPRAGUE DAWLEY RAT; TANDEM MASS SPECTROMETRY; TIME FACTOR;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; CHROMATOGRAPHY, LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; FEMALE; HEPCIDINS; INHIBITORY CONCENTRATION 50; IRON; MACACA FASCICULARIS; MALE; MEMBRANE PROTEINS; RATS; RATS, SPRAGUE-DAWLEY; TANDEM MASS SPECTROMETRY; TIME FACTORS;

EID: 84931564592     PISSN: None     EISSN: 15507416     Source Type: Journal    
DOI: 10.1208/s12248-015-9770-4     Document Type: Article

References (20)

1. Weiss G. Pathogenesis and treatment of anaemia of chronic disease. Blood Rev. 2002;16(2):87–96.
2. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–23.
3. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of mammalian iron metabolism. Cell. 2010;142(1):24–38.
4. Niederkofler V, Salie R, Arber S. Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest. 2005;115(8):2180–6.
5. Wilson NH, Key B. Neogenin: one receptor, many functions. Int J Biochem Cell Biol. 2007;39(5):874–8.
6. Meynard D, Kautz L, Darnaud V, Canonne-Hergaux F, Coppin H, Roth MP. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet. 2009;41(4):478–81.
7. Lee DH, Zhou LJ, Zhou Z, Xie JX, Jung JU, Liu Y, et al. Neogenin inhibits HJV secretion and regulates BMP-induced hepcidin expression and iron homeostasis. Blood. 2010;115(15):3136–45.
8. Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y, Samad TA, et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet. 2006;38(5):531–9.
9. Fung E, Nemeth E. Manipulation of the hepcidin pathway for therapeutic purposes. Haematologica. 2013;98(11):1667–76.
10. Rochette L, Gudjoncik A, Guenancia C, Zeller M, Cottin Y, Vergely C. The iron-regulatory hormone hepcidin: a possible therapeutic target? Pharmacol Ther 2014 Sep 7.
11. Xiao JJ, Krzyzanski W, Wang YM, Li H, Rose MJ, Ma M, et al. Pharmacokinetics of anti-hepcidin monoclonal antibody Ab 12B9m and hepcidin in cynomolgus monkeys. AAPS J. 2010;12(4):646–57.
12. Mueller BK, Yamashita T, Schaffar G, Mueller R. The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system. Philos Trans R Soc Lond B Biol Sci. 2006;361(1473):1513–29.
13. NCBI. HomoleGene: 17060. Gene conserved in Euteleostomi. NCBI 2014 September 11Available from: URL: http://www.ncbi.nlm.nih.gov/homologene/17060.
14. Bancroft JD. Theory and practice of histological techniques. 6 ed. Elsevier Limited; 2008.
15. Hall AP, Davies W, Stamp K, Clamp I, Bigley A. Comparison of computerized image analysis with traditional semiquantitative scoring of Perls’ Prussian blue stained hepatic iron deposition. Toxicol Pathol. 2013;41(7):992–1000.
16. Ludwiczek S, Theurl I, Artner-Dworzak E, Chorney M, Weiss G. Duodenal HFE expression and hepcidin levels determine body iron homeostasis: modulation by genetic diversity and dietary iron availability. J Mol Med (Berl). 2004;82(6):373–82.
17. Waring JF, Liguori MJ, Luyendyk JP, Maddox JF, Ganey PE, Stachlewitz RF, et al. Microarray analysis of lipopolysaccharide potentiation of trovafloxacin-induced liver injury in rats suggests a role for proinflammatory chemokines and neutrophils. J Pharmacol Exp Ther. 2006;316(3):1080–7.
18. Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30(1):207–10.
19. Bragdon B, Moseychuk O, Saldanha S, King D, Julian J, Nohe A. Bone morphogenetic proteins: a critical review. Cell Signal. 2011;23(4):609–20.
20. Sieber C, Kopf J, Hiepen C, Knaus P. Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev. 2009;20(5-6):343–55.