PHASE III TRIAL OF TETRATHIOMOLYBDATE IN INITIAL HEPATIC WILSON'S DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们过去的研究已经导致FDA批准锌用于肝豆状核变性的维持治疗。锌现在可以取代毒性大得多的青霉胺和曲恩汀。当威尔逊病患者首次出现铜中毒疾病时，锌的作用太慢了。这些患者可能是脑损伤或肝脏损伤的急性或慢性疾病。对于表现为脑(神经)发育的患者，我们正在开发一种安全、快速和有效的新药四硫钼酸(TM)。 然而，目前还没有关于确定最佳方法来治疗最初出现肝病的患者的工作，这些患者是由肝豆状核变性的铜中毒引起的，并出现了肝脏问题。经验性地，我们使用曲安汀和锌的组合来治疗这些患者。我们已经治疗了9名患者，每一名患者都已康复。现在，我们相信通过对这些患者进行TM治疗，我们可以取得更大的成就。TM在拯救铜中毒的绵羊方面取得了巨大的成功，否则这些绵羊就会死于肝功能衰竭。我们有机会治疗了一名威尔逊病患者，他入院时既有神经系统症状，又有肝功能衰竭，使用TM治疗，该患者的肝功能恢复速度是接受曲安替丁和锌治疗的9名患者的两倍。 我们将包括所有患者(包括儿童)，包括男性和女性，所有种族在这项研究中。他们将被随机分配到TM、曲宁组或青霉胺组。所有患者也将接受锌治疗。患者将在密歇根大学医院的综合临床研究中心住大约6周，然后在家里再接受18周的药物治疗。每周将在家中抽血进行持续评估。24周后，患者将接受锌维持治疗。 如果这项研究表明TM是治疗这类患者的一种更好的治疗方法，它将缩短患者的风险期，允许更多的患者保留自己的肝脏，而不是接受肝脏移植，并挽救供体肝脏以挽救其他生命。它还可能减少永久性肝损伤和由此导致的并发症。

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. Our past research has led to the development of an FDA approval of zinc for maintenance therapy of Wilson's disease. Zinc can now replace penicillamine and trientine, which have much more toxicity. Zinc is too slow acting for treating Wilson's disease patients when they first present with copper toxicity illness. These patients may be acutely or chonically ill from brain damage or liver damage. For the patients presenting with brain (neurologic) development, we are well along on developing a new drug, tetrathiomolybdate (TM), which is safe, fast-acting, and effective. However, no work has been done on identifying the best way to treat patients who intially present with liver disease from copper toxicity in Wilson's disease, and have developed liver problems. Empirically, we have used a combination of trientine and zinc to treat these patients. We have treated nine patients and in each case, they have recovered. Now, we believe we can accomplish even more with TM treatment of these patients. TM is dramatically successful in saving copper poisoned sheep, who otherwise die of liver failure. We had occasion to treat one Wilson's disease patient who came in with both neurologic symptoms and liver failure with TM, and the liver function recovered twice as fast in that patient as in the nine treated with trientine and zinc. We will include all patients (including children), both males and females, all ethnic groups in this study. They will be randomly assigned to TM, trientine, or penicillamine therapy. All patients will receive zinc as well. Patients will be in the General Clinical Research Center of University of Michigan Hospital for about 6 weeks, then receive the drugs at home for another 18 weeks. Blood will be drawn every week at home for continuing evaluation. After 24 weeks, patients will be placed on zinc maintenance therapy. If this study shows TM to be a superior treatment for this kind of patient, it will decrease the risk period for the patient, allow more patients to retain their own livers, as opposed to receiving a liver transplant, and save donor livers to save other lives. It may also decrease the amount of permanent liver damage and resulting complications.'