Treatment of Wilson's disease with ammonium tetrathiomolybdate. I. Initial therapy in 17 neurologically affected patients

Arch Neurol. 1994 Jun;51(6):545-54. doi: 10.1001/archneur.1994.00540180023009.

Abstract

Objective: To test the efficacy and toxicity of a new drug, ammonium tetrathiomolybdate, in the initial treatment of a relatively large series of patients presenting with neurologic signs and symptoms caused by Wilson's disease. The key aspect of efficacy was to preserve the neurologic function present at the onset of therapy.

Design: An open study of 17 patients treated for 8 weeks each. Neurologic function was evaluated by frequent quantitative neurologic and speech examinations. Several copper-related variables were studied to evaluate the effect of the drug on copper, and a large number of biochemical and clinical variables were studied to evaluate potential toxicity. Patients were then followed up at yearly intervals, with follow-up periods of 1 to 5 years reported.

Setting: A university hospital referral setting

Intervention: Patients were generally treated for 8 weeks with tetrathiomolybdate, followed by zinc maintenance therapy.

Main outcome measures: Neurologic function was evaluated by quantitative neurologic and speech examinations.

Results: None of the patients suffered a loss of neurologic function. Copper status and potential further toxic effects were generally well controlled quickly. No toxic effects resulted from administration of tetrathiomolybdate. During the ensuing period of follow-up of 1 to 5 years, neurologic recovery in most patients was good to excellent.

Conclusions: Tetrathiomolybdate appears to be an excellent form of initial treatment in patients with Wilson's disease presenting with neurologic signs and symptoms. In contrast to penicillamine therapy, initial treatment with tetrathiomolybdate does not result in further, often irreversible neurologic deterioration.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Copper / blood
  • Female
  • Hepatolenticular Degeneration / blood
  • Hepatolenticular Degeneration / complications
  • Hepatolenticular Degeneration / drug therapy*
  • Humans
  • Male
  • Molybdenum / therapeutic use*
  • Nervous System Diseases / complications
  • Trichloroacetic Acid / metabolism

Substances

  • Trichloroacetic Acid
  • Copper
  • Molybdenum
  • tetrathiomolybdate