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

Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria. Here we report that the small molecule elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Through this mechanism, elesclomol prevented detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse—a murine model of severe Menkes disease. Thus, elesclomol holds promise for the treatment of Menkes and associated disorders of hereditary copper deficiency.

Source: ScienceNOW - May 6, 2020 Category: Science Authors: Guthrie, L. M., Soma, S., Yuan, S., Silva, A., Zulkifli, M., Snavely, T. C., Greene, H. F., Nunez, E., Lynch, B., De Ville, C., Shanbhag, V., Lopez, F. R., Acharya, A., Petris, M. J., Kim, B.-E., Gohil, V. M., Sacchettini, J. C. Tags: Medicine, Diseases r-articles Source Type: news