Nav: Home

Scientists discover potential therapy for human copper metabolism disorders

July 31, 2018

COLLEGE STATION - Individuals with defects in copper metabolism may soon have more targeted treatment options thanks to a discovery by a research team led by Dr. Vishal Gohil of Texas A&M AgriLife Research in College Station.

A paper in the Proceedings of the National Academy of Sciences at http://www.pnas.org/content/early/2018/07/17/1806296115 reports that an investigational anticancer-drug, elesclomol, can restore the production of cytochrome oxidase protein complex, a critical copper-dependent enzyme required for mitochondrial energy production.

The discovery is vital since copper is an essential trace metal necessary for survival. Copper is found in all body tissues and plays a critical role in a variety of physiological processes, including energy production, detoxification of harmful free radicals, connective tissue maturation, neurotransmitter biosynthesis and brain development.

Copper metabolism deficiencies have been linked to genetic disorders such as Menkes disease, which affects infants and young children and results in deterioration of the nervous system and failure to fully develop.

The research was led by Gohil, an associate professor in the department of biochemistry and biophysics at Texas A&M University in College Station, and his graduate student, Shivatheja Soma, who worked collaboratively with scientists at the Marine Biological Laboratory, the University of Maryland, the University of Saskatchewan in Canada and the Department of Drug Discovery and Biomedical Sciences in South Carolina.

"Copper is an essential micronutrient required for mitochondrial energy production," Gohil said. "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."

Gohil said a prior attempt to treat patients with these mutations by direct copper supplementation was not successful, possibly because of inefficient copper delivery to the mitochondria.

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

The study utilized multiple model organisms to test the efficacy of elesclomol in rescuing copper deficiency. In particular, a zebrafish model of copper deficiency developed by Dr. Andrew Latimer, a research scientist at the Marine Biological Laboratory in Massachusetts, was vital in showing the efficacy of elesclomol in a vertebrate animal. Additionally, the authors directly demonstrated the therapeutic potential of elesclomol in human patient cells with genetic mutations that impair copper delivery to cytochrome oxidase.

The research involved testing several copper-binding pharmacological agents for their ability to restore mitochondrial function in a yeast model. Among these compounds, they found elesclomol was unique in that it was efficacious at low nanomolar concentrations without exhibiting overt toxicity at higher concentrations.

According to the scientists, these findings reveal that elesclomol can mimic the missing transporters of copper, which provide the potential opportunity to treat 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.
-end-
For more information on Gohil's lab, visit http://www.gohillab.com/. https://youtu.be/luDPh82wpjw

Texas A&M AgriLife Communications

Related Copper Articles:

High-performance sodium ion batteries using copper sulfide
Researchers presented a new strategy for extending sodium ion batteries' cyclability using copper sulfide as the electrode material.
Matrix could ensure vital copper supplies
Researchers have identified a matrix of risks that the mining industry must overcome to unlock vitally important copper reserves.
Do microbes control the formation of giant copper deposits?
One of the major issues when studying ore deposits formed in surficial or near-surface environments is the relationship between ore-forming processes and bacteria.
Copper compound as promising quantum computing unit
Chemists at Friedrich Schiller University in Jena (Germany) have now synthesised a molecule that can perform the function of a computing unit in a quantum computer.
Copper ions flow like liquid through crystalline structures
Materials scientists have sussed out the physical phenomenon underlying the promising electrical properties of a class of materials called superionic crystals through the investigation of CuCrSe2.
A copper bullet for tuberculosis
Tuberculosis is a sneaky disease, and the number one cause of death from infectious disease worldwide.
Copper stearate proved to be promising for heavy oil oxidation
Copper salts have found place in many industries, from pharmaceutics to agriculture, but they are rarely seen in petrochemistry and petroleum extraction.
Scientists fill in a piece of the copper transport puzzle
Researchers have identified the protein that carries copper into mitochondria, where copper is required for the functioning of the cell's energy conversion machinery.
Light and copper catalysis improves amine synthesis
EPFL chemists have developed a novel and efficient method to make amines, which are among the most important structural compounds in pharmaceuticals and organic materials.
Ink from ancient Egyptian papyri contains copper
Until recently, it was assumed that the ink used for writing was primarily carbon-based at least until the fourth and fifth centuries AD.
More Copper News and Copper Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.