According to a paper in the Proceedings of the National Academy of Sciences, a research team led by Dr. Vishal Gohil of Texas A&M AgriLife Research in College Station has now offered more targeted treatment options for individuals with defects in copper metabolism. The paper reports on an investigational anticancer-drug, by the name of Elesclomol, that has the ability to restore the production of cytochrome oxidase protein complex; a crucial copper-dependent enzyme needed for mitochondrial energy production. "Through a targeted search for copper-binding compounds, we identified elesclomol, an investigational anti-cancer drug, as the most efficient copper delivery agent," explains Gohil.
The researchers work is critical since copper is crucial for trace metal that is necessary for survival. Copper is present in all body tissues and plays an important role in multiple physiological processes, including the production of energy, detoxification of harmful free radicals, maturation of connective tissue, neurotransmitter biosynthesis, and neuro-development.
Deficiencies metabolizing copper has been linked to genetic disorders such as Wilsons disease and Menkes disease, which affects infants and young children. "Copper is an essential micronutrient required for mitochondrial energy production," says Gohil, an associate professor in the department of biochemistry and biophysics at Texas A&M University in College Station. "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." A prior attempt to treat patients with these mutations by direct copper supplementation was proven unsuccessful, which according to Gohil, might have been due to inefficient copper delivery to the mitochondria.
The research study examined many model organisms to test how effective the drug Elesclomol in treating copper deficiency. Additionally, a scientist at the Marine Biological Laboratory of Massachusetts Dr. Andrew Latimer, developed a zebrafish model of copper deficiency, which showed the vital effectiveness of Elesclomol in a vertebrate animal. Researchers also demonstrated the therapeutic potential of Elesclomol in cultured human patient cells exhibiting genetic mutations that impair the ability of copper to be delivered to cytochrome oxidase. The research involved testing copper-binding pharmacological agents for their ability to restore mitochondrial function in a yeast model. Through this testing, the researchers identified Elesclomol, which was found unique in its ability to exert its effect at such a low nanomolar concentration without the toxicity at higher concentrations. The research findings show that this particular drug can copy the missing transporters of copper, inspiring treatment options for human disorders of copper metabolism. "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.
Source: Science Daily