The use of copper-lowering therapy with tetrathiomolybdate in medicine

Expert Opinion on Investigational Drugs

Volumn 18, Issue 1, 2009, Pages 89-97

  Brewer, George J ^a  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

Alzheimer's disease therapy; Anticopper therapy; Autoimmune disease therapy; Cancer therapy; Fibrotic disease therapy; Inflammatory disease therapy; Tetrathiomolybdate; Wilson's disease therapy

Indexed keywords

CLIOQUINOL; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; PENICILLAMINE; PIRFENIDONE; TETRATHIOMOLYBDIC ACID; THALIDOMIDE; TRIENTINE; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; URSODEOXYCHOLIC ACID; ZINC;

ADVANCED CANCER; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ALZHEIMER DISEASE; ANEMIA; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; AUTOIMMUNE DISEASE; BILIARY CIRRHOSIS; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CHONDROSARCOMA; CLINICAL TRIAL; COLORECTAL CANCER; CROHN DISEASE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FATALITY; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; FIBROSING ALVEOLITIS; FOOD AND DRUG ADMINISTRATION; HEAD AND NECK CANCER; HUMAN; INFLAMMATORY DISEASE; KIDNEY CANCER; LEUKOPENIA; LIVER FIBROSIS; LUNG FIBROSIS; MESOTHELIOMA; MYELOMA; NAUSEA AND VOMITING; NEUROLOGIC DISEASE; NONHUMAN; PHARMACODYNAMICS; PRIMARY BILIARY CIRRHOSIS; PROSTATE CANCER; PSORIASIS; RETINA MACULA AGE RELATED DEGENERATION; RETINA NEOVASCULARIZATION; REVIEW; RHEUMATOID ARTHRITIS; SIDE EFFECT; SQUAMOUS CELL CARCINOMA; TREATMENT DURATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; WILSON DISEASE;

ANIMALS; CLINICAL TRIALS AS TOPIC; COPPER; DISEASE; DRUG EVALUATION, PRECLINICAL; DRUG TOLERANCE; HUMANS; MOLYBDENUM;

EID: 67649371133     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543780802621859     Document Type: Review

References (72)

1. Brewer GJ, Dick RD, Yuzbasiyan-Gurkan V, et al. Initial therapy of patients with Wilson's disease with tetrathiomolybdate. Arch Neurol 1991;48:42-47
2. Brewer GJ, Dick RD, Johnson V, et al. Treatment of Wilson's disease with ammonium tetrathiomolybdate. I. Initial therapy in 17 neurologically affected patients. Arch Neurol 1994;51:545-554
3. Brewer GJ, Johnson V, Dick RD, et al. Treatment of Wilson disease with ammonium tetrathiomolybdate. II. Initial therapy in 33 neurologically affected patients and follow-up with zinc therapy. Arch Neurol 1996;53:1017-1025
4. 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
5. 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 •• This is an important paper because it confirms the low rate of neurologic worsening with tetrathiomolybdate, in a double-blind setting, and for the first time presents data on the high rate of neurologic worsening with trientine.
6. Scheinberg IH, Sternlieb I. Wilson's disease. In: Smith LHJ, editor. Major problems in internal medicine. Philadelphia: WB Saunders; 1984. p 1-171
7. Brewer GJ. Wilson's disease: a clinician's guide to recognition, diagnosis, and management. Boston: Kluwer Academic Publishers; 2001
8. th edition. New York: McGraw-Hill; 2008. p. 2449-2452
9. Walshe JM. Penicillamine, a new oral therapy for Wilson's disease. Am J Med 1956;21:487-495
10. Walshe JM. Treatment of Wilson's disease with trientine (triethylene tetramine) dihydrochloride. Lancet 1982;1:643-647 (Pubitemid 12179933)
11. Brewer GJ, Terry CA, Aisen AM, et al. Worsening of neurologic syndrome in patients with Wilson's disease with initial penicillamine therapy. Arch Neurol 1987;44:490-493 (Pubitemid 17061929)
12. Brewer GJ, Dick RD, Johnson VD, et al. Treatment of Wilson's disease with zinc: XV long-term follow-up studies. J Lab Clin Med 1998;132:264-278 (Pubitemid 28490259)
13. Brewer GJ, Ullenbruch MR, Dick RB, et al. Tetrathiomolybdate therapy protects against bleomycin-induced pulmonary fibrosis in mice. J Lab Clin Med 2003;141:210-216 (Pubitemid 36324239)
14. Brewer GJ, Dick R, Ullenbruch MR, et al. Inhibition of key cytokines by tetrathiomolybdate in the bleomycin model of pulmonary fibrosis. J Inorg Biochem 2004;98:2160-2167 (Pubitemid 39488145)
15. Askari FK, Dick RB, Mao M, et al. Tetrathiomolybdate therapy protects against concanavalin A and carbon tetrachloride hepatic damage in mice. Exp Bio Med 2004;229:857-863 (Pubitemid 39166492)
16. 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 • This paper presents a comprehensive study of hepatic fibrosis prevention by tetrathiomolybdate in an excellent mouse model, and demonstrates suppression of numerous gene activities involved in inflammation and fibrosis. (Pubitemid 351574799)
17. Ma S, Hou G, Dick RD, et al. Tetrathiomolybdate protects against liver injury from acetaminophen in mice. J Appl Res Clin Exp Ther 2004;4:419-426 (Pubitemid 39299386)
18. Hou G, Dick R, Abrams GD, et al. Tetrathiomolybdate protects against cardiac damage by doxorubicin in mice. J Lab Clin Med 2005;146:299-303 (Pubitemid 41464407)
19. McCubbin MD, Hou G, Abrams GD, et al. Tetrathiomolybdate is effective in a mouse model of arthritis. J Rheumatol 2006;33:2501-2506 • This study shows not only suppression by tetrathiomolybdate of the arthritis in this mouse model, but inhibition of the excessive oxidant stress produced in the model. (Pubitemid 46067832)
20. Brewer GJ, Dick R, Zeng C, et al. 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
21. Hou G, Abrams G, Dick R, et al. Efficacy of tetrathiomolybdate in a mouse model of multiple sclerosis. Transl Res 2008;152:239-244
22. Pan Q, Bao LW, Merajver SD. Tetrathiomolybdate inhibits angiogenesis and metastasis through suppression of the NFkappaB signaling cascade. Mol Cancer Res 2003;1:701-706 (Pubitemid 37025588)
23. Pan Q, Kleer CG, van Golen KL, et al. Copper deficiency induced by tetrathiomolybdate suppresses tumor growth and angiogenesis. Cancer Res 2002;62:4854-4859 (Pubitemid 34984403)
24. Cox C, Merajver SD, Yoo S, et al. Inhibition of the growth of squamous cell carcinoma by tetrathiomolybdate-induced copper suppression in a murine model. Arch Otolaryngol Head Neck Surg 2003;129:781-785 (Pubitemid 36858968)
25. Cox CD, Teknos TN, Barrios M, et al. The role of copper suppression as an antiangiogenic strategy in head and neck squamous cell carcinoma. Laryngoscope 2001;111:696-701 (Pubitemid 32295286)
26. Kent MS, Madewell BR, Dank G, et al. An anticopper antiangiogenic approach for advanced cancer in spontaneously occurring tumors, using tetrathiomolybdate: A pilot study in a canine animal mode. J Trace Elem Exp Med 2004;17:9-20 (Pubitemid 38129759)
27. Hassouneh B, Islam M, Nagel T, et al. Tetrathiomolybdate promotes tumor necrosis and prevents distant metastases by suppressing angiogenesis in head and neck cancer. Mol Cancer Res 2007;6:1039-1045 (Pubitemid 46554574)
28. 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 (Pubitemid 30064969)
29. 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 (Pubitemid 36554589)
30. 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
31. Pass HI, Brewer GJ, Dick R, et al. A Phase II trial of tetrathiomolybdate after surgery for malignant mesothelioma: final results. Ann Thorac Surg 2008;86:383-389 •• This paper is important because it provides preliminary evidence of efficacy for tetrathiomolybdate in cancer, and is the only clinical study so far of a trial in minimal, if not micrometastatic, disease. (Pubitemid 351978017)
32. 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 2008
33. Tian XL, Yao W, Guo ZJ, et al. Low dose pirfenidone suppresses transforming growth factor beta-1 and tissue inhibitor of metalloproteinase-1, and protects rats from lung fibrosis induced by bleomycina. Chin Med Sci J 2006;21:145-151 (Pubitemid 44637968)
34. Lindor K. Ursodeoxycholic acid for the treatment of primary biliary cirrhosis. N Engl J Med 2007;357:1524-1529 (Pubitemid 47572638)
35. Shanahan JC, St Clair W. Tumor necrosis factor-alpha blockade: a novel therapy for rheumatic disease. Clin Immunol 2002;103:231-242
36. D'Haens G, Van Deventer S, Van Hogezand R, et al. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: a European multicenter trial. Gastroenterology 1999;116:1029-1034 (Pubitemid 29203012)
37. Ogilvie AL, Antoni C, Dechant C, et al. Treatment of psoriatic arthritis with antitumour necrosis factor-alpha antibody clears skin lesions of psoriasis resistant to treatment with methotrexate. Br J Dermatol 2001;144:587-589 (Pubitemid 32232017)
38. Brewer GJ. Copper lowering therapy with tetrathiomolybdate produces antiangiogenic, anticancer, antifibrotic and antiinflammatory effects. Semin Integr Med 2003;1:181-190 (Pubitemid 39345202)
39. Breitkreutz I, Anderson KC. Thalidomide in multiple myeloma-clinical trials and aspects of drug metabolism and toxicity. Expert Opin Drug Metab Toxicol 2008;4:973-985
40. Harousseau JL. New treatments in multiple myeloma: beyond optimal treatment. Ann Oncol 2008;19(Suppl 5):v68-70
41. Raza A, Mehdi M, Mumtaz M, et al. Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Cancer 2008;113:1596-1604
42. Hideshima T, Raje N, Richardson PG, et al. A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Ther Clin Risk Manag 2008;4:129-136
43. McCormack PL, Keam SJ. Spotlight on bevacizumab in metastatic colorectal cancer. BioDrugs 2008;22:339-341
44. Birk D, Barbato J, Mureebe L, et al. Current insights on the biology and clinical aspects of VEGF regulation. Vasc Endovascular Surg 2008 [Epub ahead of print]
45. Mills CF, El-Gallad TT, Bremner I. Effects of molybdate, sulfide, and tetrathiomolybdate on copper metabolism in rats. J Inorg Biochem 1981;14:189-207 (Pubitemid 11063055)
46. Bremner I, Mills CF, Young BW. Copper metabolism in rats given di- or trithiomolybdates. J Inorg Biochem 1982;16:109-119
47. Mills CF, El-Gallad TT, Bremner I, et al. Copper and molybdenum absorption by rats given ammonium tetrathiomolybdate. J Inorg Biochem 1981;14:163-175 (Pubitemid 11120306)
48. Gooneratne SR, Howell JM, Gawthorne JM. An investigation of the effects of intravenous administration of thiomolybdate on copper metabolism in chronic Cu-poisoned sheep. Br J Nutr 1981;46:469-480 (Pubitemid 12213841)
49. Gooneratne SR, Christensen DA. Effect of chelating agents on the excretion of copper, zinc and iron in the bile and urine of sheep. Vet J 1997;153:171-178 (Pubitemid 27363919)
50. Ogra Y, Ohmichi M, Suzuki KT. Systemic dispositions of molybdenum and copper after tetrathiomolybdate injection in LEC rats. J Trace Elem Med Bio 1995;9:165-169
51. Sugawara N, Lai YR, Sugawara C. Therapeutic effects of tetrathiomolybdate on hepatic dysfunction occurring naturally in Long-Evans Cinnamon (LEC) rats: a bona fide animal model for Wilson's disease. Res Commun Mol Pathol Pharmacol 1999;103:177-187 (Pubitemid 29383632)
52. Omoto A, Kawahito Y, Prudovsky I, et al. Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats. Arthritis Res Ther 2005;7:R1174-82 [Epub 2005 Aug 8]
53. van Golen KL, Bao L, Brewer GJ, et al. Suppression of tumor recurrence and metastasis by a combination of the PHSCN sequence and the antiangiogenic compound tetrathiomolybdate in prostate carcinoma. Neoplasia 2002;4:373-379 (Pubitemid 34976952)
54. Elner SG, Elner VM, Yoshida A, et al. Effects of tetrathiomolybdate in a mouse model of retinal neovascularization. Invest Ophthalmol Vis Sci 2005;46:299-303 (Pubitemid 40041211)
55. Huang X, Atwood CS, Hartshorn MA, et al. The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 1999;38:7609-7616 (Pubitemid 29289332)
56. Multhaup G, Schlicksupp A, Hesse L, et al. The amyloid precursor protein of Alzheimer's disease in the reduction of copper(II) to copper(I). Science 1996;271:1406-1409 (Pubitemid 26089474)
57. Angeletti B, Waldron KJ, Freeman KB, et al. BACE1 cytoplasmic domain interacts with the copper chaperone for superoxide dismutase-1 and binds copper. J Biol Chem 2005;280:17930-17937 (Pubitemid 41389034)
58. Ma Q, Li Y, Du J, et al. Copper binding properties of a tau peptide associated with Alzheimer's disease studied by CD, NMR, and MALDI-TOF MS. Peptides 2006;27:841-849
59. Sparks DL, Schreurs BG. Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease. Proc Natl Acad Sci USA 2003;100:11065-11069 (Pubitemid 37140153)
60. Squitti R, Pasqualetti P, Dal Forno G, et al. Excess of serum copper not related to ceruloplasmin in Alzheimer disease. Neurology 2005;64:1040-1046 (Pubitemid 40388458)
61. Adlard PA, Cherny RA, Finkelstein DI, et al. Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron 2008;59:43-55 (Pubitemid 351905863)
62. Wadsworth TL, Bishop JA, Domes CM, et al. Copper complexing with tetrathiomolybdate in a murine model of Alzheimer's Disease. Society for Neuroscience Annual Meeting, San Diego, CA; 2007
63. Flaherty KR, Arenberg DA, White ES, et al. Treatment of idiopathic pulmonary fibrosis with tetrathiomolybdate. Submitted for publication
64. Brewer GJ, Merajver SD. Cancer therapy with tetrathiomolybdate: antiangiogenesis by lowering body copper - a review. Integr Cancer Ther 2002;1:327-337 (Pubitemid 37107843)
65. 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 (Pubitemid 37039358)
66. Squitti R, Rossini PM, Cassetta E, et al. d-penicillamine reduces serum oxidative stress in Alzheimer's disease patients. Eur J Clin Invest 2002;32:51-59 (Pubitemid 36228383)
67. Haywood S, Dincer Z, Jasani B, et al. Molybdenum-associated pituitary endocrinopathy in sheep treated with ammonium tetrathiomolybdate. J Comp Pathol 2004;130:21-31 (Pubitemid 38185949)
68. Ke Y, Symonds HW. The effect of molybdenum compounts on the biliary excretion of copper by sheep. Proc Nutr Soc 1987;46:69a
69. Mason J, Lamand M, Tressol JC, et al. Studies of the changes in systemic copper metabolism and excretion produced by the intravenous administration of trithiomolybdate in sheep. Br J Nutr 1988;59:289-300 (Pubitemid 18101098)
70. Humphries WR, Mills CF, Greig A, et al. Use of ammonium tetrathiomolybdate in the treatment of copper poisoning in sheep. Vet Rec 1986;119:596-598 (Pubitemid 17226373)
71. Humphries WR, Morrice PC, Bremner I. A convenient method for the treatment of chronic copper poisoning in sheep using subcutaneous ammonium tetrathiomolybdate. Vet Rec 1988;123:51-53 (Pubitemid 18172389)
72. Medici V, Trevisan CP, Bigotto MA, et al. Adverse reaction after tetrathiomolybdate treatment for Wilson's disease: a case report. Mov Disord 2006;21:2030-2032 (Pubitemid 44848968)