Medici Valentina, Sturniolo Giacomo Carlo
University of California, Davis, Division of Gastroenterology and Hepatology, Department of Internal Med, 4150 V Street, Suite 3500, Sacramento, CA 95817, USA.
IDrugs. 2008 Aug;11(8):592-606.
Tetrathiomolybdate (TTM) is a copper chelator that has also demonstrated antiangiogenic, antifibrogenic and anti-inflammatory actions in preclinical studies. The drug, from the University of Michigan was licensed to Pipex Pharmaceuticals Inc for development for several indications; development of the drug for cancer was later licensed to Attenuon LLC. In a phase III clinical trial, TTM stabilized neurological function in patients with Wilson disease, causing significant recovery in 81% of patients at 3 years post initiation of therapy; a second phase III trial was ongoing at the time of publication. A phase I/II clinical trial demonstrated the efficacy of TTM in patients with idiopathic pulmonary fibrosis, and led the FDA to grant TTM Orphan Drug status for this disease. Several phase II clinical trials had also been completed in patients with various cancers, and revealed mixed efficacy. TTM was also assessed in a phase I clinical trial for age-related macular degeneration, but the results reported from the trial were negative; no further development has occurred for this indication. TTM was assessed for the treatment of psoriasis in a phase II clinical trial, but no data have been reported. At the time of publication, phase II and phase III clinical trials were ongoing in patients with Alzheimer's disease and primary biliary cirrhosis, respectively. The most common clinical side effects observed for TTM over the range of indications have been anemia, neutropenia, leukopenia and transaminase elevations. These side effects were generally resolved with either a dose adjustment or temporary suspension of the dosing regimen. TTM is predicted to most likely find a niche in the therapy of Wilson disease, for which current treatment options are limited.
四硫钼酸盐（TTM）是一种铜螯合剂，在临床前研究中也已显示出抗血管生成、抗纤维化和抗炎作用。这种来自密歇根大学的药物已授权给Pipex制药公司开发用于多种适应症；后来其癌症治疗药物的开发又授权给了Attenuon有限责任公司。在一项III期临床试验中，TTM使威尔逊病患者的神经功能稳定，在治疗开始3年后，81%的患者有显著恢复；在发表时第二项III期试验正在进行。一项I/II期临床试验证明了TTM对特发性肺纤维化患者的疗效，并促使美国食品药品监督管理局（FDA）授予TTM针对该疾病的孤儿药地位。针对多种癌症患者的几项II期临床试验也已完成，结果显示疗效不一。TTM还在一项针对年龄相关性黄斑变性的I期临床试验中进行了评估，但该试验报告的结果为阴性；该适应症未再有进一步开发。TTM在一项II期临床试验中被评估用于治疗银屑病，但尚未有数据报告。在发表时，针对阿尔茨海默病和原发性胆汁性肝硬化患者的II期和III期临床试验正在分别进行。在所有适应症范围内观察到的TTM最常见的临床副作用是贫血、中性粒细胞减少、白细胞减少和转氨酶升高。这些副作用通常通过调整剂量或暂时停止给药方案得以解决。预计TTM最有可能在威尔逊病的治疗中找到一席之地，因为目前针对该病的治疗选择有限。
