Methanobactin rapidly facilitates biliary copper excretion in a Wilson disease rat model visualised by Cu PET/MRI.

Background And Purpose: Methanobactins are peptides with high copper affinity and potential to treat Wilson disease. We examined how two methanobactins (ARBM101 and MB-OB3b) affected copper handling in the LPP Atp7b Wilson disease rat model, compared to penicillamine or saline, by Cu positron emission tomography/magnetic resonance imaging. Heterozygotes served as controls.

Diagnosing Wilson Disease in Acute Liver Failure: Comparison of Existing and Experimental Biomarkers.

Introduction: In acute liver failure due to Wilson disease (ALF-WD), early and correct diagnosis is critical. Readily available biochemical parameters, e.g.

Relative Exchangeable Copper, Exchangeable Copper and Total Copper in the Diagnosis of Wilson Disease.

Background And Aims: Diagnosing Wilson disease (WD) remains challenging. The exchangeable copper (CuEXC) methodology measures the non-ceruloplasmin-bound copper fraction in serum. Relative exchangeable copper (REC), the ratio of CuEXC to total serum copper (Total Cu), has been proposed as a potential diagnostic biomarker.

Exchangeable serum copper: Adult and pediatric reference intervals and in vitro stability in a nordic cohort.

Wilson disease (WD) is a rare genetic disorder characterized by copper overload, primarily affecting the liver and brain, and the organ damage is believed to be caused by non-ceruloplasmin-bound copper (NCC). Accurate and early diagnosis is important for prognosis. Recently, a method for the measurement of NCC, exchangeable serum copper (CuEXC), was developed and shown to be a promising marker of WD, especially as the fraction of total copper, relative exchangeable copper (REC).

Effects of trientine and penicillamine on intestinal copper uptake: A mechanistic 64 Cu PET/CT study in healthy humans.

Background And Aims: Trientine (TRI) and D-penicillamine (PEN) are used to treat copper overload in Wilson disease. Their main mode of action is thought to be through the facilitation of urinary copper excretion. In a recent study, TRI was noninferior to PEN despite lower 24-hour urinary copper excretion than PEN.

Effects of tetrathiomolybdate on copper metabolism in healthy volunteers and in patients with Wilson disease.

Background & Aims: In Wilson disease (WD), copper accumulates in the liver and brain causing disease. Bis-choline tetrathiomolybdate (TTM) is a potent copper chelator that may be associated with a lower risk of inducing paradoxical neurological worsening than conventional therapy for neurologic WD. To better understand the mode of action of TTM, we investigated its effects on copper absorption and biliary excretion.

Distribution of non-ceruloplasmin-bound copper after i.v. Cu injection studied with PET/CT in patients with Wilson disease.

Background & Aims: In Wilson disease (WD), copper accumulation and increased non-ceruloplasmin-bound copper in plasma lead to liver and brain pathology. To better understand the fate of non-ceruloplasmin-bound copper, we used PET/CT to examine the whole-body distribution of intravenously injected 64-copper (Cu).

Methods: Eight patients with WD, five heterozygotes, and nine healthy controls were examined by dynamic PET/CT for 90 min and static PET/CT up to 20 h after injection.

Positron Emission Tomography Using 64-Copper as a Tracer for the Study of Copper-Related Disorders.

Copper is an essential trace element, functioning in catalysis and signaling in biological systems. Radiolabeled copper has been used for decades in studying basic human and animal copper metabolism and copper-related disorders, such as Wilson disease (WD) and Menke's disease. A recent addition to this toolkit is 64-copper (Cu) positron emission tomography (PET), combining the accurate anatomical imaging of modern computed tomography (CT) or magnetic resonance imaging (MRI) scanners with the biodistribution of the Cu PET tracer signal.

Case report: Huppke-Brendel syndrome in an adult, mistaken for and treated as Wilson disease for 25 years.

Background: Huppke-Brendel (HB) syndrome is an autosomal recessive disease caused by variants in the gene. Since 2012, less than ten patients have been reported, none survived year six. With neurologic involvement and ceruloplasmin deficiency, it may mimic Wilson disease (WD).

Effect of oral zinc regimens on human hepatic copper content: a randomized intervention study.

Zinc inhibits intestinal copper uptake, an effect utilized for treating Wilson's disease (WD). We used copper-64 (Cu) PET/CT to examine how much four weeks of treatment with different zinc regimens reduced the hepatic Cu content after oral Cu administration and test if alternative regimens were noninferior to the standard regimen of zinc acetate 50 mg × 3 daily. Forty healthy persons were randomized to four different zinc protocols.

Cognitive impairment in stable Wilson disease across phenotype.

In Wilson disease (WD), mutations in the gene encoding the ATP7B copper transport protein causes accumulation of copper especially in liver and brain. WD typically presents with hepatic and/or neuropsychiatric symptoms. Impaired cognition is a well-described feature in patients with neurological WD, while the reports on cognition in hepatic WD patients are fewer and less conclusive.