Recent advances in Wilson disease.

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.