Study Detects Early ALS in Mice Using Blood Levels of Copper Isotopes

Measuring copper concentration in the blood may allow for the diagnosis of amyotrophic lateral sclerosis (ALS) before the onset of clinical symptoms, according to new research in mice. The study, developed by researchers at the University of Wollongong in Australia, might provide a new means for ALS diagnosis that does not require disease progression into the onset of symptoms, which would allow patients to begin treatment at earlier stages.

The findings were recently presented at the Goldschmid conference in Yokohama, Japan, in a presentation titled “Copper Isotope Metallomics and Amyotrophic Lateral Sclerosis.”

“While this work is only preliminary and applies to a specific mouse model of ALS, it is the first of its kind on this pathology and brings hope that one day we could use isotopic measurement in blood samples as an early detection tool of the disease,” said Prof. Anthony Dosseto from the University of Wollongong in a press release.

ALS is a neurodegenerative disease characterized by progressive degeneration of the motor neurons. Since the disease develops well before symptoms do, diagnostic markers that help detect ALS at an early stage might improve the future development of new treatment options.

Some forms of familial ALS are caused by mutations that are thought to destabilize copper (Cu) binding to the Cu, zinc superoxide dismutase 1 (SOD1) protein.

Here, the researchers used an ALS mouse model to measure the association between copper, zinc, and iron concentrations and ALS onset and progression. Their results demonstrated that ALS mice had increased levels of the three trace elements in the muscles, compared to normal mice. Copper was also increased in the spinal cord.

Importantly, although the blood copper levels were similar in ALS and normal mice, the researchers found that the ratio between copper isotopes (65Cu/63Cu) was different in both groups. It is not known if the changes are a cause or a consequence of the disease, but the increase in the trace elements in the muscle, spinal cord, and blood was found before the appearance of clinical symptoms.

This suggests that measuring the copper isotope ratio in a blood-based test might have an important diagnostic value, as it would be able to detect the presence of the disease before clinical symptoms appear.

“Biomedical applications of geochemical methods — especially high precision isotope analyses — have barely been explored. This is the latest study hinting at the exciting possibilities,” said Prof. Ariel Anbar from the Howard Hughes Medical Institute at Arizona State University.