title: Tracing copper-thiomolybdate complexes in a prospective treatment for Wilson's disease.
abstract: Wilson's disease is a human genetic disorder which results in copper accumulation in liver and brain. Treatments such as copper chelation therapy or dietary supplementation with zinc can ameliorate the effects of the disease, but if left untreated, it results in hepatitis, neurological complications, and death. Tetrathiomolybdate (TTM) is a promising new treatment for Wilson's disease which has been demonstrated both in an animal model and in clinical trials. X-ray absorption spectroscopy suggests that TTM acts as a novel copper chelator, forming a complex with accumulated copper in liver. We have used X-ray absorption spectroscopy and X-ray fluorescence imaging to trace the molecular form and distribution of the complex in liver and kidney of an animal model of human Wilson's disease. Our work allows new insights into metabolism of the metal complex in the diseased state.
authors.affiliation: Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E2, Canada.
authors.forename: Limei
authors.initials: L
authors.lastname: Zhang
authors.forename: Josef
authors.initials: J
authors.lastname: Lichtmannegger
authors.forename: Karl H
authors.initials: KH
authors.lastname: Summer
authors.forename: Samuel
authors.initials: S
authors.lastname: Webb
authors.forename: Ingrid J
authors.initials: IJ
authors.lastname: Pickering
authors.forename: Graham N
authors.initials: GN
authors.lastname: George
mesh_terms: D000251:Adenosine Triphosphatases / Q000172:deficiency / Q000235:genetics; D000818:Animals; D027682:Cation Transport Proteins / Q000172:deficiency / Q000235:genetics; D002614:Chelating Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D004195:Disease Models, Animal; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008982:Molybdenum / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D011446:Prospective Studies; D051381:Rats; D020332:Rats, Inbred LEC; D011922:Rats, Mutant Strains
chemical_list: D027682:Cation Transport Proteins; D002614:Chelating Agents; D003300:Copper; D008982:Molybdenum; C020809:tetrathiomolybdate; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases