Progress in Neurotherapeutics and Neuropsychopharmacology

Table of Contents - 2008 - Volume 3, Issue 01  


Tetrathiomolybdate versus Trientine in the Initial Treatment of Neurologic Wilson's Disease

George J. Brewer a1c1, Fred Askari a2, Matthew T. Lorincz a3, Martha Carlson a4, Michael Schilsky a5, Karen J. Kluin a6, Peter Hedera a7, Paolo Moretti a8, John K. Fink a9, Roberta Tankanow a10, Robert B. Dick a11 and Julia Sitterly a12
a1 Department of Human Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Email: brewergj@umich.edu
a2 Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Email: faskari@med.umich.edu
a3 Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Email: lorincz@umich.edu
a4 Department of Pediatrics-Neurology, University of Michigan, Ann Arbor, MI, USA; Email: marthac@umich.edu
a5 Department of Internal Medicine, Cornell University, New York, NY, USA; Email: mls2003@med.cornell.edu
a6 Department of Neurology, Department of Speech Pathology, University of Michigan, Ann Arbor, MI, USA; Email: niulk@umich.edu
a7 Department of Neurology, Vanderbilt University, Nashville, TN, USA; Email: peter.hedera@Vanderbilt.Edu
a8 Departments of Neurology and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Email: pmoretti@bcm.tmc.edu
a9 Department of Neurology, University of Michigan, Ann Arbor, MI, USA; Email: jkfink@umich.edu
a10 College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; Email: robertat@umich.edu
a11 Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Email: bobdick@umich.edu
a12 Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Email: sitterly@umich.edu

Article author query
brewer gj   [PubMed][Google Scholar] 
askari f   [PubMed][Google Scholar] 
lorincz mt   [PubMed][Google Scholar] 
carlson m   [PubMed][Google Scholar] 
schilsky m   [PubMed][Google Scholar] 
kluin kj   [PubMed][Google Scholar] 
hedera p   [PubMed][Google Scholar] 
moretti p   [PubMed][Google Scholar] 
fink jk   [PubMed][Google Scholar] 
tankanow r   [PubMed][Google Scholar] 
dick rb   [PubMed][Google Scholar] 
sitterly j   [PubMed][Google Scholar] 

ABSTRACT

Background: The initial treatment of the neurologic presentation of Wilson's disease is problematic. Penicillamine, used for years on most patients, causes neurologic worsening in up to half of such patients, and half of those who worsen never recover. Zinc, ideal for maintenance therapy, is too slow for these acutely ill patients. We have developed tetrathiomolybdate (TM) for this type of patient, and it has worked well in open label studies. Trientine, another anticopper drug on the market approved for penicillamine intolerant patients, had not been tried in this type of patient. Here, we report on a double blind trial of TM versus trientine in the neurologically presenting Wilson's disease patient. Design and Methods: The study was a double blind design in which patients received either TM plus zinc, or trientine plus zinc, for 8 weeks 1 Patients were accepted if they presented with neurologic symptoms from Wilson's disease, if they had not been treated longer than 4 weeks with penicillamine or trientine. Patients were followed in the hospital for the 8 weeks of treatment with weekly semiquantitative neurologic and speech examinations, to evaluate possible neurologic worsening. They also had blood and urine studies done weekly. At discharge from hospital they were continued on zinc maintenance therapy, and returned at yearly intervals for 3 years for further evaluation. Results: Twenty-three patients were entered into the trientine arm and 6 reached criteria for neurologic deterioration, while 25 patients were entered into the TM arm and only 1 deteriorated (p < 0.05). One patient on trientine had an adverse event while 7 on TM had adverse events. All adverse events were mild. Four patients in the trientine arm died during follow-up, 3 having shown initial neurologic deterioration, 2 patients in the TM arm died. In those patients who did not deteriorate or die, neurologic and speech recovery over 3 years was good. Interpretation: TM is a superior choice to trientine for the initial therapy of neurologic Wilson's disease.


Key Words: copper toxicity; double blind trial; neurologic damage; tetrathiomolybdate; trientine; Wilson's disease.

Correspondence:
c1 Correspondence should be addressed to: George J. Brewer, MD, Department of Human Genetics and Department of Internal Medicine, University of Michigan Medical School, 5024 Kresge Bldg. II, Ann Arbor, MI 48109-0534, USA; Ph: +1 734 764 5499; Fax: +1 734 615 2048; Email: brewergj@umich.edu

Footnotes

1 This study was originally published in reference 1.