At the European Bioanalysis Forum (EBF) conference in November 2021, Quotient Sciences [1] and Orphalan [2] presented a poster describing a comparative analysis of a novel method for calculating serum non-ceruloplasmin-bound copper (NCC) levels in patients with Wilson disease (WD).
WD is a genetic disorder of copper transport, which can be diagnosed and monitored using serum NCC levels. During a Phase I clinical trial of a potential new treatment for WD, the US Food and Drug Administration (FDA) highlighted that the current standard method of determining NCC levels, NCC-EDTA, may underestimate NCC levels. As a result, Orphalan developed a novel assay to determine NCC levels using copper protein speciation (NCC-CuSp) and liquid chromatography with inductively coupled plasma mass spectrometry (LC-ICP-MS). The aim of the project was to compare NCC values obtained from the novel NCC-CuSp assay and the standard NCC-EDTA assay in WD patients.
During the clinical trial, the WD patients had blood samples taken at regular intervals, and serum NCC levels were evaluated by both the NCC-CuSp and NCC-EDTA methods. Paired data was compared using a Bland–Altman plot (difference plot), which is a statistical method used to analyze the agreement between two different assays.
The overall level of agreement between the NCC-EDTA and NCC-CuSp methods from all paired samples and across the complete range of values obtained from the WD patients was moderate. On average, the NCC-EDTA values were found to be lower than the NCC-CuSp values. This project highlighted how imprecise measurements of NCC levels may lead to inappropriate medication titration in WD patients.
Poster authors
1. Quotient Sciences: S. McDougall
2. Orphalan: T. Morley, O. Kamlin
3. National Measurement Laboratory at LGC: H. Goenaga-Infante, E. Del Castillo
4. International Drug Development Institute: K. D’Hollander
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