TY - JOUR T1 - Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101164 VL - 5 IS - 3 SP - e202101164 AU - Sabine Borchard AU - Stefanie Raschke AU - Krzysztof M Zak AU - Carola Eberhagen AU - Claudia Einer AU - Elisabeth Weber AU - Sandra M Müller AU - Bernhard Michalke AU - Josef Lichtmannegger AU - Albrecht Wieser AU - Tamara Rieder AU - Grzegorz M Popowicz AU - Jerzy Adamski AU - Martin Klingenspor AU - Andrew H Coles AU - Ruth Viana AU - Mikkel H Vendelbo AU - Thomas D Sandahl AU - Tanja Schwerdtle AU - Thomas Plitz AU - Hans Zischka Y1 - 2022/03/01 UR - https://www.life-science-alliance.org/content/5/3/e202101164.abstract N2 - In Wilson disease, excessive copper accumulates in patients’ livers and may, upon serum leakage, severely affect the brain according to current viewpoints. Present remedies aim at avoiding copper toxicity by chelation, for example, by D-penicillamine (DPA) or bis-choline tetrathiomolybdate (ALXN1840), the latter with a very high copper affinity. Hence, ALXN1840 may potentially avoid neurological deterioration that frequently occurs upon DPA treatment. As the etiology of such worsening is unclear, we reasoned that copper loosely bound to albumin, that is, mimicking a potential liver copper leakage into blood, may damage cells that constitute the blood-brain barrier, which was found to be the case in an in vitro model using primary porcine brain capillary endothelial cells. Such blood–brain barrier damage was avoided by ALXN1840, plausibly due to firm protein embedding of the chelator bound copper, but not by DPA. Mitochondrial protection was observed, a prerequisite for blood–brain barrier integrity. Thus, high-affinity copper chelators may minimize such deterioration in the treatment of neurologic Wilson disease. ER -