Translational Research
Volume 155, Issue 3 , Pages 123-130 , March 2010

Treatment of primary biliary cirrhosis with tetrathiomolybdate: results of a double-blind trial

  • Fred Askari

      Affiliations

    • Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich
    • ,
  • Dawna Innis

      Affiliations

    • Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich
    • ,
  • Robert B. Dick

      Affiliations

    • Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich
    • ,
  • Guoqing Hou

      Affiliations

    • Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich
    • ,
  • Jorge Marrero

      Affiliations

    • Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich
    • ,
  • Joel Greenson

      Affiliations

    • Department of Pathology, University of Michigan Medical School, Ann Arbor, Mich
    • ,
  • George J. Brewer

      Affiliations

    • Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich
    • Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Mich
    • Corresponding Author InformationReprint requests: George J. Brewer, MD, Department of Human Genetics, University of Michigan Medical School, G061X MBNI, Ann Arbor, MI 48109-5720

Received 10 August 2009 ,Revised 22 September 2009 ,Accepted 23 September 2009.

References 

  1. Brewer GJ, Hedera P, Kluin KJ, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy. Arch Neurol. 2003;60:379–385
  2. Brewer GJ, Askari F, Lorincz MT, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson disease. Arch Neurol. 2006;63:521–527
  3. Brewer GJ. Copper lowering therapy with tetrathiomolybdate as an antiangiogenic strategy in cancer. Curr Cancer Drug Targets. 2005;5:195–202
  4. Brewer GJ, Dick RD, Grover DK, et al. Treatment of metastatic cancer with tetrathiomolybdate, an anticopper, antiangiogenic agent: phase I study. Clin Cancer Res. 2000;6:1–10
  5. Pass HI, Brewer GJ, Dick R, Carbone M, Merajver S. A phase II trial of tetrathiomolybdate after surgery for malignant mesothelioma: final results. Ann Thorac Surg. 2008;86:383–389
  6. Brewer GJ, Ullenbruch MR, Dick RB, Olivarez L, Phan SH. Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in mice. J Lab Clin Med. 2003;141:210–216
  7. Brewer GJ, Dick R, Ullenbruch MR, Jin H, Phan SH. Inhibition of key cytokines by tetrathiomolybdate in the bleomycin model of pulmonary fibrosis. J Inorg Biochem. 2004;98:2160–2167
  8. Askari FK, Dick RB, Mao M, Brewer GJ. Tetrathiomolybdate therapy protects against concanavalin A and carbon tetrachloride hepatic damage in mice. Exp Bio Med. 2004;229:857–863
  9. Ma S, Hou G, Dick RD, Brewer GJ. Tetrathiomolybdate protects against liver injury from acetaminophen in mice. J Appl Res Clin Exp Ther. 2004;4:419–426
  10. Song M, Song Z, Barve S, et al. Tetrathiomolybdate protects against bile duct ligation-induced cholestatic liver injury and fibrosis. J Pharmacol Exp Ther. 2008;325:409–416
  11. Flaherty KR, Arenberg DA, White ES, et al. Treatment of idiopathic pulmonary fibrosis with tetrathiomolybdate. In press.
  12. Hou G, Dick R, Abrams GD, Brewer GJ. Tetrathiomolybdate protects against cardiac damage by doxorubicin in mice. J Lab Clin Med. 2005;146:299–303
  13. Brewer GJ, Dick R, Zeng C, Hou G. The use of tetrathiomolybdate in treating fibrotic, inflammatory, and autoimmune diseases, including the non-obese diabetic mouse model. J Inorg Biochem. 2006;100:927–930
  14. McCubbin MD, Hou G, Abrams GD, Dick R, Zhang Z, Brewer GJ. Tetrathiomolybdate is effective in a mouse model of arthritis. J Rheumatol. 2006;33:2501–2506
  15. Hou G, Abrams G, Dick R, Brewer GJ. Efficacy of tetrathiomolybdate in a mouse model of multiple sclerosis. Transl Res. 2008;152:239–244
  16. Chung RT, Podolsky DK. Cirrhosis and its complications: primary biliary cirrhosis. In:  Braunwald E,  Fauci AS,  Kasper DL,  Hauser SL,  Longo DL,  Jameson JL editor. Harrison's principles of internal medicine. 15th ed. New York: McGraw-Hill; 2001;p. 1757–1758
  17. Digestive Disease Interagency Coordinating Committee. Translational research in primary biliary cirrhosis. Available at: http://www2.niddk.nih.gov/NR/rdonlyres/8FC7A357-1BA5-4068-9B6D-AA012EA3FD3D/0/DDICC_June_16_2003_Minutes.pdf. Accessed November 19, 2007.
  18. Pyrsopoulos NT, Reddy KR, Wu GY, et al. Primary biliary cirrhosis. Available at: http://www.emedicine.com/MED/topic223.htm. Accessed December 11, 2008.
  19. Colucci G, Schaffner F, Paronetto F. In situ characterization of the cell-surface antigens of the mononuclear cell infiltrate and bile duct epithelium in primary biliary cirrhosis. Clin Immunol Immunopathol. 1986;41:35–42
  20. Kaplan MM. Primary biliary cirrhosis. N Engl J Med. 1996;335:1570–1580
  21. Lindor K. Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. N Engl J Med. 2007;357:1524–1529
  22. Gartner EM, Griffith KA, Pan Q, et al. A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer. Invest New Drugs. 2009;27:159–165
  23. Henry NL, Dunn R, Merjaver S, et al. Phase II trial of copper depletion with tetrathiomolybdate as an antiangiogenesis strategy in patients with hormone refractory prostate cancer. Oncology. 2006;71:168–175
  24. Redman BG, Esper P, Pan Q, et al. Phase II trial of tetrathiomolybdate in patients with advanced kidney cancer. Clin Cancer Res. 2003;9:1666–1672
  25. Vine AK, Brewer GJ. Tetrathiomolybdate as an antiangiogenesis therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration. Trans Am Ophthalmol Soc. 2002;100:73–76

 Supported by Grant FD-02590-02 from the U.S. Food and Drug Administration's Orphan Products Office, the General Clinical Research Center of the University of Michigan Hospitals, Grant MO1-RR000042 from the National Institutes of Health, and Grant Ul1-RR024986 Clinical and Translational Science Awards.

PII: S1931-5244(09)00296-5

doi: 10.1016/j.trsl.2009.09.009

Translational Research
Volume 155, Issue 3 , Pages 123-130 , March 2010

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