RT Journal Article SR Electronic T1 Bis-choline tetrathiomolybdate prevents copper-induced blood–brain barrier damage JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202101164 DO 10.26508/lsa.202101164 VO 5 IS 3 A1 Borchard, Sabine A1 Raschke, Stefanie A1 Zak, Krzysztof M A1 Eberhagen, Carola A1 Einer, Claudia A1 Weber, Elisabeth A1 Müller, Sandra M A1 Michalke, Bernhard A1 Lichtmannegger, Josef A1 Wieser, Albrecht A1 Rieder, Tamara A1 Popowicz, Grzegorz M A1 Adamski, Jerzy A1 Klingenspor, Martin A1 Coles, Andrew H A1 Viana, Ruth A1 Vendelbo, Mikkel H A1 Sandahl, Thomas D A1 Schwerdtle, Tanja A1 Plitz, Thomas A1 Zischka, Hans YR 2022 UL http://www.life-science-alliance.org/content/5/3/e202101164.abstract AB 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.