Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice. Academic Article uri icon


  • 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.

published proceedings

  • Science

altmetric score

  • 73.35

author list (cited authors)

  • Guthrie, L. M., Soma, S., Yuan, S., Silva, A., Zulkifli, M., Snavely, T. C., ... Sacchettini, J. C.

citation count

  • 32

complete list of authors

  • Guthrie, Liam M||Soma, Shivatheja||Yuan, Sai||Silva, Andres||Zulkifli, Mohammad||Snavely, Thomas C||Greene, Hannah Faith||Nunez, Elyssa||Lynch, Brogan||De Ville, Courtney||Shanbhag, Vinit||Lopez, Franklin R||Acharya, Arjun||Petris, Michael J||Kim, Byung-Eun||Gohil, Vishal M||Sacchettini, James C

publication date

  • May 2020