tetrathiomolybdate and Nervous-System-Diseases

Wilson's disease is a rare autosomal recessive disease of copper accumulation and copper toxicity, due to mutations in the ATP7B gene, which leads to a failure of copper excretion in the bile. It presents clinically primarily as liver disease, psychiatric disease, neurological disease, or a combination of these. The neurological disease is a movement disorder, with abnormalities of speech, tremor, incoordination and dystonia being common features. Diagnosis of neurologically presenting patients is usually straightforward, with Kayser-Fleischer rings and a urine copper over 100 microg/day almost invariably present. In the treatment of neurologically presenting patients, penicillamine should always be avoided, because of the high risk of permanent, drug-induced, additional neurological deterioration. A new drug we have developed, tetrathiomolybdate, given for 8-16 weeks, in combination with zinc, is our first choice for treating these patients. In the absence of availability of tetrathiomolybdate, zinc or trientine are the next best choices.

Topics: Behavior; Chelating Agents; Enzyme Inhibitors; Hepatolenticular Degeneration; Humans; Molybdenum; Nervous System Diseases; Penicillamine; Trientine; Zinc

It is unclear what anticopper drug to use for patients with Wilson disease who present with neurologic manifestations because penicillamine often makes them neurologically worse and zinc is slow acting.. To evaluate the frequency of neurologic worsening and drug adverse effects with ammonium tetrathiomolybdate.. Open-label study of 55 untreated patients (22 of them new) presenting with neurologic Wilson disease treated with tetrathiomolybdate varying from 120 to 410 mg/d for 8 weeks and then followed up for 3 years. Neurologic function was assessed with scored neurologic and speech tests.. A university hospital referral setting.. All untreated, newly diagnosed patients with neurologic Wilson disease.. Treatment with tetrathiomolybdate.. Neurologic function was evaluated by neurologic and speech examinations. Drug adverse effects were evaluated by complete blood cell counts and biochemical measures.. Only 2 (4%) of 55 patients treated with tetrathiomolybdate showed neurologic deterioration, compared with an estimated 50% of penicillamine-treated patients. Five of the 22 new patients exhibited bone marrow suppression and 3 had aminotransferase elevations. These numbers are higher than in the original 33 patients and appear to be due primarily to a more rapid dose escalation.. Tetrathiomolybdate shows excellent efficacy in patients with Wilson disease who present with neurologic manifestations. With rapid escalation of dose, adverse effects from bone marrow suppression or aminotransferase elevations can occur.

Topics: Adult; Child; Enzyme Inhibitors; Female; Follow-Up Studies; Hepatolenticular Degeneration; Humans; Male; Molybdenum; Nervous System Diseases; Neurologic Examination; Treatment Outcome; Zinc

Topics: Dimercaprol; Hepatolenticular Degeneration; Humans; Molybdenum; Nervous System Diseases; Penicillamine

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.. 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.. 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 speech examinations.. 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.. 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.

Topics: Adolescent; Adult; Copper; Female; Hepatolenticular Degeneration; Humans; Male; Molybdenum; Nervous System Diseases; Trichloroacetic Acid