Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice

Abstract

Elesclomol rescues Menkes disease mice Menkes disease results from loss-of-function mutations in the P-type copper-transporting adenosine triphosphatase ATP7A. Children diagnosed with Menkes present with connective tissue abnormalities and neurodegenerative changes that result in death caused by severe copper deficiency, typically before 3 years of age. In the brain, lack of copper impairs cytochrome c oxidase (complex IV) in the electron transport chain, which leads to progressive neurological injury in Menkes patients. No treatment exists for Menkes disease because of the difficulty in supplying the brain with copper using traditional hydrophilic copper complexes such as copper histidine. Guthrie et al. developed a treatment involving the drug elesclomol that successfully alleviated disease symptoms in a mouse model of Menkes disease (see the Perspective by Lutsenko). Science , this issue p. 620 ; see also p. 584