Moini Maryam, To Uyen, Schilsky Michael L
Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Division of Gastroenterology, University of Toronto, Toronto, Canada.
Transl Gastroenterol Hepatol. 2021 Apr 5;6:21. doi: 10.21037/tgh-2020-02. eCollection 2021.
Wilson disease (WD) is rare genetic disorder that presents with varied phenotype that can at times make the diagnosis challenging. Medical treatments are available, but there are still unmet needs for patients. Since life-long therapy is necessary, adherence to medical therapy and best practices for monitoring and individualizing therapy continue to evolve. Studies are ongoing that address some of these issues. In the current review we focused our attention to recent advances in the diagnosis of WD, current medical treatments, future potential therapies and treatment monitoring. We include discussion of new methodology for detection and quantitation of ophthalmologic signs of WD, new brain imaging modalities for early detection of neurologic involvement in patients and potential new diagnostic methodology using blood samples that may be applicable to newborn screening and adult disease diagnosis. In addition, there are new strategies aimed at improving adherence and outcomes with currently available therapies, including once daily chelation dosing and discussion of the efficacy of different zinc salt compounds. With respect to new therapies with different mechanisms of action, we discuss studies on Bis-choline tetrathiomolybdate (TTM) in patients, pre-clinical studies of a novel chelator methanobactin and other animal studies exploring cures for WD with gene therapy using adeno-associated vectors (AAVs) that introduce into liver cells. There are also promising advances in the more accurate measurement of non-ceruloplasmin bound copper and exchangeable copper in the circulation which would potentially help with monitoring and individualization of treatment and possibly play a role in future disease diagnosis.
威尔逊病（WD）是一种罕见的遗传性疾病，其表现出的多种表型有时会使诊断具有挑战性。虽然有可用的医学治疗方法，但患者仍有未满足的需求。由于需要终身治疗，坚持药物治疗以及监测和个体化治疗的最佳实践仍在不断发展。针对其中一些问题的研究正在进行中。在当前的综述中，我们将注意力集中在WD诊断的最新进展、当前的医学治疗、未来的潜在疗法以及治疗监测上。我们讨论了检测和定量WD眼部体征的新方法、用于早期检测患者神经受累的新脑成像模式以及可能适用于新生儿筛查和成人疾病诊断的使用血液样本的潜在新诊断方法。此外，还有旨在提高现有疗法的依从性和治疗效果的新策略，包括每日一次的螯合给药以及不同锌盐化合物疗效的讨论。关于具有不同作用机制的新疗法，我们讨论了双胆碱四硫代钼酸盐（TTM）在患者中的研究、新型螯合剂甲醇菌素的临床前研究以及其他使用腺相关病毒（AAV）将基因导入肝细胞来探索WD治疗方法的动物研究。在更准确测量循环中未与铜蓝蛋白结合的铜和可交换铜方面也有了有前景的进展，这可能有助于治疗的监测和个体化，并且可能在未来疾病诊断中发挥作用。
