Elesclomol Can Help Restore Copper Levels in Patients with Mitochondrial Diseases, Researchers Find

Elesclomol, an investigational anti-cancer drug, can help treat patients with mitochondrial diseases by restoring copper in the mitochondria, a new study shows.

The study, “Elesclomol restores mitochondrial function in genetic models of copper deficiency,” was published in the journal Proceedings of the National Academy of Sciences.

Mitochondria are known as the powerhouses of the cell, producing most of the energy used to carry out cellular activities.

Copper is a vital nutrient required for the assembly and activity of cytochrome c oxidase (CcO) — the last enzyme of the energy production pathway in the mitochondria.

“Copper is an essential micronutrient required for mitochondrial energy production,” Vishal Gohil, MD, an associate professor in the department of biochemistry and biophysics at Texas A&M University, said in a press release. “Inherited mutations that prevent copper delivery to a key mitochondrial enzyme perturb energy production and result in fatal mitochondrial disease. Currently, no therapy exists for these disorders.”

Researchers have determined that copper supplementation can help fight CcO deficiency in cells from patients with mutations that stop copper delivery.

However, clinical studies have shown that supplementation with copper did not improve clinical outcomes or survival, possibly because of inefficient copper delivery to the mitochondria.

Thus, researchers set out to identify compounds that can efficiently transport copper across biological membranes.

Through the use of a yeast cell model of copper deficiency, researchers tested and were able to identify a compound  — elesclomol (ES)  — that can re-establish copper balance in copper-deficient cells.

“Through a targeted search for copper-binding compounds, we identified elesclomol, an investigational anti-cancer drug, as the most efficient copper delivery agent,” Gohil said.

Results indicated that ES is at least 1,000 times more potent than copper in mitigating the mitochondrial growth defect observed in yeast coa6Δ cells. The researchers showed that ES was able to do so with a range of mutations, suggesting broad applicability.

Next, researchers showed that ES supplementation improved levels of CcO subunits in human cell lines that have genetic defects in copper metabolism.

Using zebrafish models, they showed that ES can alleviate copper deficiency in intact living vertebrate animals.

ES is under investigation for treatment of certain cancers. “Elesclomol has undergone multiple human clinical trials; thus our findings offer an exciting possibility of repurposing this anti-cancer drug for the treatment of copper metabolism disorders,” Gohil said.

The authors wrote that these results “suggest that ES could be efficacious in the treatment of more common disorders of copper deficiency, including Menkes disease.”