Biomarkers for neurological disease identified in teeth

Dental Tribune International

Wed. 27. May 2020

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NEW YORK, U.S./ANN ARBOR, Mich., U.S.: Mount Sinai scientists have identified biological markers present in childhood that relate to the degenerative and often fatal neurological disease called amyotrophic lateral sclerosis (ALS), also known Lou Gehrig’s disease. The researchers found the markers in the teeth of patients who went on to develop ALS as adults.

ALS is a condition that usually manifests in individuals during their fifth or sixth life decade. The cause is not known, and there is no test to predict its onset. So far, genetic studies have not been able to unveil much information, and whereas experts believe environmental factors play a significant role in the development of the disease, there have been no clear indications of which ones play this role. For the study, the researchers used lasers to map the growth rings that form daily in teeth and discovered that patients with ALS metabolized metals in a different way to the way in which patients without the disease did.

“This is the first study to show a clear signature at birth and within the first decade of life, well before any clinical signs or symptoms of the disease,” said senior author Prof. Manish Arora from the Icahn School of Medicine at Mount Sinai in New York. “We hope in the long term, after validation of this work in larger studies, that this will lead to preventive strategies. What’s exciting about this work is that we are looking at biological pathways that we could potentially modify with drug development.”

The study revealed a dysregulated uptake of a mixture of essential elements, including zinc and copper, as well as toxins like lead and tin, in 36 ALS patients compared with 31 controls. The markers of metal uptake dysregulation were also observed in teeth from an ALS mouse model that also showed differences in the distribution of metals in the brain compared with controls.

“Our previous work showed that the dysregulation of elemental metabolism in early life was associated with the onset of neurological disease such as autism and ADHD,” explained Dr. Christine Austin, who is an assistant professor in the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai and who was greatly involved in contributing to this work. “This study shows that metabolic dysregulation is also associated with neurological conditions with a much greater lag to symptom onset,” she added.

Researchers at the University of Michigan played an important role in this study, and their clinics provided samples and data from ALS patients and patients in the control group. “Genetic studies have yielded important contributions to our understanding of ALS, but they do not tell the complete story,” said study co-investigator Dr. Eva Feldman, director of the ALS Center of Excellence at Michigan Medicine.

The study, titled “Early life metal dysregulation in amyotrophic lateral sclerosis,” was published online on May 21, 2020, in Annals of Clinical and Translational Neurology, ahead of inclusion in an issue.

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