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.