title: Tetrathiomolybdate as an antiangiogenesis therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration.
abstract: OBJECTIVE
  Since previous studies have shown that angiogenesis requires copper, this study assessed the efficacy and safety of oral tetrathiomolybdate, an antiangiogenesis drug that binds copper, in subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration.
  
  
  METHODS
  This phase I trial involved 10 patients with age-related active subfoveal CNV. After patient consent was obtained and initial laboratory tests were performed, patients were given a loading dose of tetrathiomolybdate, followed by a maintenance dose to maintain serum ceruloplasmin (Cp) levels at 5 to 15 mg/dL. Serum Cp levels are a surrogate marker of copper status. Patient follow-up consisted of a detailed protocol that included best corrected visual acuity, measurement of extent of CNV (both classic and occult) on fluorescein angiograms, and laboratory tests to ensure that anemia did not develop. The study was approved by the institutional review board of the University of Michigan Medical Center and by the Food and Drug Administration.
  
  
  RESULTS
  Follow-up of the 10 patients ranged from 4 to 12 months. The targeted serum Cp level was achieved in 8 of the 10 patients. Initially, patients showed stabilization of CNV, but with continued follow-up, all patients showed progression of CNV and loss of visual acuity. Initial mean visual acuity was 20/60; final mean visual acuity was 20/131. At completion of the study, 2 patients showed about a 25% increase in CNV, 1 patient a 60% increase, 1 patient a 100% increase, and 6 patients a 700% to 1,600% increase in CNV.
  
  
  CONCLUSIONS
  At the dosages used in this study, tetrathiomolybdate was ineffective in preventing the progression of CNV secondary to age-related macular degeneration.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan Medical Center, Ann Arbor, USA.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Vine
authors.forename: George J
authors.initials: GJ
authors.lastname: Brewer
mesh_terms: D000284:Administration, Oral; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002570:Ceruloplasmin / Q000032:analysis; D020256:Choroidal Neovascularization / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005584:Fovea Centralis; D006801:Humans; D008268:Macular Degeneration / Q000097:blood / Q000150:complications*; D008297:Male; D008982:Molybdenum / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D008982:Molybdenum; C020809:tetrathiomolybdate; D002570:Ceruloplasmin