OHSU

Pilot Project Abstract - Lutsenko, Svetlana, PhD

Lutsenko, Svetlana, PhD, Associate Professor, Dept. of Biochemistry and Molecular Biology, OHSU:

“Characterization of a copper carrier in the urine of Atp7b-/- mice and Wilson disease patients"

Copper is essential for normal human metabolism; disruption of copper homeostasis result is severe disorders, such as Wilson disease (WD). WD is caused by mutations in the copper-transporting ATPase ATP7B and is associated with toxic accumulation of copper in the liver. An early diagnosis is essential for successful treatment of WD. However, timely diagnosis is often challenging, because the manifestations of the disease are diverse and non-specific. None of the currently available tests, alone, identifies WD with certainty. New non-invasive tests that increase the specificity of WD detection and point to the stage of the disease will be highly beneficial. Recent genetic and biochemical studies led to a better understanding of the molecular basis of copper metabolism. However, it remains unknown which molecule(s) “sense” and regulate copper status at the organism level. We have recently discovered that in Atp7b-/- mice, an animal model of WD, copper is excreted into the urine in a complex with a small copper carrier (SCC), which facilitates the removal of excess copper from the body via kidney when liver function is compromised. The major goals of the proposed research are to isolate SCC from the urine of Atp7b-/- mice, verify the presence of SCC in WD patients, and determine whether SCC can be utilized as a predictor of the stage of pathology development in WD. The proposed studies represent the first step towards the development of new diagnostic/monitoring tests for WD.