PDF(Pubmed)
Abstract：
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 ATP7B 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.
摘要：
威尔逊病（WD）是罕见的遗传性疾病，表现出不同的表型，有时会使诊断具有挑战性。有医疗手段,但患者的需求仍未得到满足。因为终身治疗是必要的,坚持药物治疗以及监测和个体化治疗的最佳实践不断发展.正在进行研究，以解决其中一些问题。在当前的综述中，我们将注意力集中在WD诊断的最新进展上，目前的医疗方法，未来的潜在疗法和治疗监测。我们讨论了用于检测和定量WD眼科征象的新方法，用于早期检测患者神经系统受累的新的脑成像方式，以及使用血液样本的潜在新诊断方法，这些方法可能适用于新生儿筛查和成人疾病诊断。此外,有新的策略旨在提高目前可用疗法的依从性和结果，包括每日一次螯合给药和讨论不同锌盐化合物的功效。关于具有不同作用机制的新疗法，我们讨论了对患者的双胆碱四硫钼酸盐（TTM）的研究，一种新型螯合剂甲钴素的临床前研究和其他动物研究，探索使用将ATP7B引入肝细胞的腺相关载体（AAV）进行基因治疗治疗WD的方法。在更准确地测量循环中的非铜蓝蛋白结合铜和可交换铜方面也有有希望的进展，这可能有助于监测和个体化治疗，并可能在未来的疾病诊断中发挥作用。
