| First Author | Guthrie LM | Year | 2020 |
| Journal | Science | Volume | 368 |
| Issue | 6491 | Pages | 620-625 |
| PubMed ID | 32381719 | Mgi Jnum | J:290805 |
| Mgi Id | MGI:6436797 | Doi | 10.1126/science.aaz8899 |
| Citation | Guthrie LM, et al. (2020) Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice. Science 368(6491):620-625 |
| abstractText | 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. |
