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 Sabine Borchard A1 Stefanie Raschke A1 Krzysztof M Zak A1 Carola Eberhagen A1 Claudia Einer A1 Elisabeth Weber A1 Sandra M Müller A1 Bernhard Michalke A1 Josef Lichtmannegger A1 Albrecht Wieser A1 Tamara Rieder A1 Grzegorz M Popowicz A1 Jerzy Adamski A1 Martin Klingenspor A1 Andrew H Coles A1 Ruth Viana A1 Mikkel H Vendelbo A1 Thomas D Sandahl A1 Tanja Schwerdtle A1 Thomas Plitz A1 Hans Zischka YR 2022 UL https://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.