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Original Contribution
March 2003

Treatment of Wilson Disease With Ammonium Tetrathiomolybdate: III. Initial Therapy in a Total of 55 Neurologically Affected Patients and Follow-up With Zinc Therapy

Author Affiliations

From the Departments of Human Genetics (Dr Brewer, Mr Dick, and Ms Sitterly), Internal Medicine (Drs Brewer and Askari), and Neurology (Drs Hedera and Fink and Ms Kluin); Division of Speech-Language Pathology, Department of Physical Medicine and Rehabilitation (Ms Kluin); and Department of Pediatrics (Dr Carlson), University of Michigan, Ann Arbor. The University of Michigan has recently licensed the antiangiogenic uses of tetrathiomolybdate to Attenuon LLC, San Diego, Calif, and both Dr Brewer and Mr Dick have equity in Attenuon LLC. The authors have no relevant financial interest in this manuscript.

Arch Neurol. 2003;60(3):379-385. doi:10.1001/archneur.60.3.379

Background  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.

Objective  To evaluate the frequency of neurologic worsening and drug adverse effects with ammonium tetrathiomolybdate.

Design  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.

Setting  A university hospital referral setting.

Patients  All untreated, newly diagnosed patients with neurologic Wilson disease.

Intervention  Treatment with tetrathiomolybdate.

Main Outcome Measures  Neurologic function was evaluated by neurologic and speech examinations. Drug adverse effects were evaluated by complete blood cell counts and biochemical measures.

Results  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.

Conclusions  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.