Results in a new mouse model of ALS indicate that delivering copper to the central nervous system can be therapeutic, according to a study published in the journal Neurobiology of Disease by a research team led by Joseph Beckman, Ph.D., of Oregon State University in Covallis, Ore. The paper, titled “Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SODG93A mice co-expressing the copper-chaperone-for-SOD” is available through open access. While the treatment delivered major benefit to the mice in the experiments, it is far too soon to know whether similar treatment can help people with ALS, according to ALS experts. In any case, oral copper supplements cannot substitute for the treatment used in the study and can be highly toxic if taken beyond recommended doses.
ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. For unknown reasons, veterans are twice as likely to develop ALS as the general population. There is no cure, and only one drug approved by the U.S. Food and Drug Administration (FDA) modestly extends survival.
The study focused on the effects of increasing the amount of copper available in the central nervous system. Copper is critical for the structure and function of several important enzymes, including superoxide dismutase (SOD), mutations of which are a genetic cause of ALS. SOD receives copper from another protein, called copper chaperone for SOD (CCS).
In the new study, Joseph Beckman, Ph.D. and colleagues used mice that overexpressed both human SOD and human CCS. These mice succumb to disease much quicker than mice overexpressing only SOD, they found, probably because the high amount of CCS sequestered the mouse’s supply of copper, inducing a deficiency in the spinal cord. The researchers suspect that this prevented proper functioning of another copper-containing enzyme, called cytochrome C oxidase, which helps mitochondria release cellular energy, and this accelerated the death of motor neurons.
When Dr. Beckman and his team supplied excess copper, the mice lived far longer than untreated mice. The copper was given in a compound called CuATSM, which, unlike oral copper supplements, passes directly into the nervous system.
“These are highly intriguing, and highly encouraging, results,” said Lucie Bruijn, Ph.D., M.B.A., Chief Scientist for The ALS Association, “but whether CuATSM could be beneficial for people with ALS remains unknown.” The Association is funding studies of CuATSM in the canine model of ALS by Dr. Beckman, which is due to a naturally occurring mutation in SOD, in order to see if copper supplementation may provide benefit in a model in which the mutant gene is not highly overexpressed.
“We are eager to explore the potential of this new treatment idea,” Dr. Bruijn said. “But in the meantime, it is critical to remember that oral copper supplements do not reach the central nervous system and thus cannot provide any benefit and can be quite toxic.”