THERAPY OF WILSON'S DISEASE WITH TETRATHIOMOLYBDATE - COMPARISON WITH TRIENTINE

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。 FDA 最近批准醋酸锌，现已很好地涵盖了威尔逊病的维持治疗。然而，患有神经系统疾病的患者的初始治疗存在问题。锌的作用相当缓慢，在锌控制铜毒性之前，急症患者的疾病可能会进展。治疗威尔逊氏病使用时间最长的铜螯合剂青霉胺对这些患者来说极其危险。铜螯合剂曲恩汀的使用有限，但似乎比青霉胺的副作用更少。尽管曲恩汀存在理论上的风险，但尚未有最初恶化的报道。我们推出了一种新的孤儿药（四硫代钼酸盐，或TM）用于这些患者的初始治疗。 TM具有快速起效的理想特性，并且不会导致最初的恶化。我们进行了一项为期 3 年的 III 期双盲研究，比较 TM 与曲恩汀对神经系统患者的初始治疗。我们研究了 48 名患者，其中 25 名接受曲恩汀组，23 名接受 TM 组。要回答的主要问题是：初始神经功能恶化的速度是否存在差异？第一年和第二年的神经恢复程度有差异吗？严重副作用的发生率是否存在差异？研究完成后，我们不仅会回答有关 TM 与曲恩汀的问题，而且还会表征曲恩汀（一种已上市的药物）在初始治疗环境中的功效和毒性。

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.