EBF 2021: Novel Copper Protein Speciation Method for Calculating Serum Non Ceruloplasmin Copper: A Comparative Analysis

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• Wilson disease (WD) is an autosomal recessive disorder of copper (Cu) transport caused by mutations of the ATP7B gene
• International guidelines on the management of WD recommend serum non-ceruloplasmin-bound Cu (NCC; free Cu index) for diagnosis and therapeutic monitoring; NCC target range in WD = 50 to 150μg/L
• The current “Standard of Care” evaluation of NCC levels involves the incubation of serum with EDTA (NCC-EDTA) to chelate copper from proteins other than ceruloplasmin before ultracentrifugation
• A high molecular weight artifact binding copper from albumin retained above the 30KDa filter may result in an underestimation of true NCC
• During the conduct of an RCT (clinical trials gov: NCT03539952), the FDA highlighted the deficiencies in NCC-EDTA
• Orphalan developed and optimized a novel assay to determine NCC using copper protein speciation (NCC-CuSp) with LC-ICP-MS
• The NCC-CuSpassay is a two-step process that involves:
• Inductively coupled mass spectrometry to measure total Cu
• Liquid chromatography (LC-ICP-MS) to calculate Cp-Cu as a percentage of total Cu
• LC-ICP-MS determines Cp-Cu indirectly by the speciation of Cu-containing proteins
• There are no data in WD subjects comparing the performance of NCC-CuSpwith NCC-EDTA