Treatment Of Wilson Disease Research Articles

Treatment of Wilson Disease With Ammonium Tetrathiomolybdate

To test the efficacy and toxic effects of ammonium tetrathiomolybdate in the initial treatment of a relatively large series of patients with neurologic symptoms and signs caused by Wilson disease. Two key aspects of efficacy are to preserve the neurologic function present at the onset of therapy and to maximize the opportunity for long-term recovery. An open study of 33 patients treated for 8 weeks each, including further follow-up data on the original 17 patients. Neurologic function was evaluated by frequent quantitative neurologic and speech pathology examinations. Several copper-related variables were studied to evaluate the effect of the drug on copper, and several biochemical and clinical variables were studied to evaluate potential toxic effects. Patients were then followed up at yearly intervals, with follow-up periods of 1 to 8 years reported. A university hospital referral setting. Patients were generally treated for 8 weeks with tetrathiomolybdate, followed by zinc maintenance therapy. Neurologic function was evaluated by quantitative neurologic and motor speech examinations and magnetic resonance imaging scans of the brain. During the 8 weeks of tetrathiomolybdate administration, only 1 of the 33 patients showed deterioration in neurologic function. Copper status and potential further toxic effects were generally well controlled quickly. Evaluation of data from individual patients revealed evidence of a toxic side effect in only 1 patient, who exhibited reversible anemia. During the ensuing period of follow-up of 1 to 6 years, neurologic recovery in most patients was good to excellent. Tetrathiomolybdate appears to be an excellent form of initial treatment in patients with Wilson disease who present with neurologic symptoms and signs. In contrast to penicillamine therapy, initial treatment with tetrathiomolybdate rarely allows further, often irreversible, neurologic deterioration.

D-Penicillamine and Neutrophilic Agranulocytosis

To the Editor. —Although D-penicillamine is of demonstrable value in the treatment of Wilson's disease and rheumatoid arthritis, its use has been limited by side effects. Recently, it has been debated whether a cytotoxic effect or an immunologic mechanism is responsible for the neutrophilic agranulocytosis appearing in patients treated with D-penicillamine. Corcos et al1reported that the presence of antibodies to D-penicillamine or penicillin could not be demonstrated by the Coombs' test, and that no leukocyte agglutinins were found in serum at the time agranulocytosis developed or during the recovery phase. This suggests a cytotoxic effect of D-penicillamine. These findings are supported by evidence of D-penicillamine—induced interference with the synthesis of DNA, RNA, protein, collagen, and mucopolysaccharides.2On the other hand, a positive result from a direct Coombs' test in a rheumatoid patient receiving D-penicillamine3indicates that some immunologic mechanism may be responsible for D-penicillamine—induced neutrophilic agranulocytosis.

Treatment of Wilson's disease.

Excerpt The goal of treatment of Wilson's disease is to increase copper excretion. In view of the ample evidence that the symptoms of Wilson's disease are due to damage caused by excess copper, thi...

New Oral Chelating Agent for Treatment of Wilson's Disease

THERE is some doubt1 about the relevance of abnormal copper metabolism to the pathogenesis of hepato-lenticular degeneration (Wilson's disease), but the most important aspect of therapy at present is the mobilization and excretion of tissue copper and the reduction of absorption of copper from the gastro-intestinal tract. The majority viewpoint was well expressed by Scheinberg when he wrote “… it is difficult to believe, from the evidence already at hand, that chronic copper toxicity is not the basis of this disease”2. At the present time, the cupruretic drug of choice is penicillamine (ββ-dimethylcysteine) first introduced in 1956 (ref. 3).