Scientists from Monai Sinai have identified biological markers that relate to neurological degenerative disease called amyotrophic lateral sclerosis. The disease is also known as Lou Gehrig’s disease or ALS.
Researchers found the markers in teeth of patients with ALS. The growth rings that form daily in the teeth were mapped and it was discovered that the rings formed at birth within the first 10 years of life of the patients with ALS. Patients with ALS metabolized metals differently compared to patients who did not have the disease.
The disease generally manifests in the 50s or 60s. The cause of the disease, however, is not known. Moreover, there is no test to predict the onset of the disease. Although genetic studies have not revealed much about the disease, experts believe that environmental factors play a significant role in the development of disease.
“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 Manish Arora, BDS, MPH, PhD, Edith J. Baerwald Professor and Vice Chair of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. “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.”
A dysregulated mixture of uptake of essential elements as well as toxins, including zinc, copper, lead and tin was seen in 36 ALS patients, on the contrary to 31 patients of the controlled group. The markers were also observed in teeth of ALS mouse model that compared to controls showed differences in the distribution of metals.
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 to 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,” said Christine Austin, PhD, Assistant Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai, a major contributor to this work. “This study shows that metabolic dysregulation is also associated with neurological conditions with a much greater lag to symptom onset”.
Data samples from ALS patients and control group were also provided by the University of Michigan.
“Genetic studies have yielded important contributions to our understanding of ALS, but they do not tell the complete story,” said study co-investigator Eva Feldman, MD, PhD, Russell N. DeJong Professor of Neurology at University of Michigan, and Director of the ALS Center of Excellence at Michigan Medicine. “Our group has previously shown a link between persistent organic pollutants and ALS risk and progression, but there is also evidence pointing to metals as an ALS risk factor. Therefore, we were very excited to work with the Mount Sinai team.”
Figueroa‐Romero et al. (2020). Early life metal dysregulation in amyotrophic lateral sclerosis. Annals of Clinical and Translational Neurology. DOI: https://doi.org/10.1002/acn3.51006