THERAPY OF WILSONS DISEASE W/ TETRATHIOMOLYBDATE COMPARISON W/ TRIENTINE

威尔森氏病的维持治疗现在很好地覆盖了最近FDA批准醋酸锌。然而，神经系统疾病患者的初始治疗是有问题的。锌的作用相当缓慢，急性病人的疾病可能在锌控制铜毒性之前进展。治疗威尔逊氏病时间最长的铜螯合剂青霉胺对这些病人来说是极其危险的。铜螯合剂曲恩汀的使用有限，但其副作用似乎比青霉胺少。最初的恶化还没有报道，尽管理论上使用曲恩汀有风险。我们推出了一种新的孤儿药（四硫钼酸盐，简称TM），用于这些患者的初始治疗。TM具有理想的快速作用特性，不会引起初始恶化。在这里，我们提出了一项为期3年，双盲，双地点的研究，比较TM和曲恩汀对神经系统疾病患者的初始治疗。我们计划对90名患者进行试验，每组45名。需要回答的主要问题是：在初始神经退化的速度上是否存在差异？第1年和第2年的神经恢复程度有差异吗？严重副作用的发生率有差异吗？在研究完成时，我们不仅回答了有关TM与曲恩汀的问题，而且还将描述曲恩汀（一种已经上市的药物）在初始治疗环境中的疗效和毒性。

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. Here we propose a 3 year, phase III double blind, two site, study comparing TM to trientine for initial therapy of neurologically presenting patients. We project a trial of 90 patients, 45 in each 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.