This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The maintenance therapy of Wilson's disease is now well covered with the recent FDA approval of zinc acetate. However, the initial therapy of patients presenting with neurologic disease is problematic. Zinc is rather slow-acting and the disease of the acutely ill patient may progress prior to zinc controlling copper toxicity. The copper chelator that has been used the longest for Wilson's disease, penicillamine, is extremely dangerous for these patients. The copper chelator, trientine, has seen limited use, but seems to have fewer side effects than penicillamine. Initial worsening has not yet been reported, although it is a theoretical risk with trientine. We have introduced a new orphan drug (tetrathiomolybdate, or TM) for the initial treatment of these patients. TM has ideal properties of fast action, and doesn't cause initial worsening. We have carried out a 3 year, phase III double blind, study comparing TM to trientine for initial therapy of neurologically presenting patients. We studied 48 patients, 25 in the trientine arm and 23 in the TM arm. The major questions to be answered are: Is there a difference in the rate of initial neurological deterioration? Is there a difference in degree of neurological recovery at years 1 and 2? Are there differences in the incidence of serious side effects? At the completion of the study, we will not only have answered the questions relating to TM vs. trientine, but we will have characterized the efficacy and toxicity of trientine, a drug already on the market, in the initial treatment setting.
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