Lead paradox could lead to new therapy for Lou Gehrig's disease

Washington, Dec 1 (ANI): Scientists have discovered that high level of lead, which is a neurotoxic heavy metal, can slow the progression of amyotrophic lateral sclerosis, or Lou Gehrig's disease-a finding that could lead to a new type of therapy for the disease.

ALS is a progressive, fatal neurodegenerative disease that causes muscle weakness and atrophy throughout the body. There is no known cure for this ailment.

The researchers from the Instituto Clemente Estable and the University of the Republic in Montevideo, Uruguay, and at Oregon State University, were surprised by the results, since lead is also a known risk factor for ALS.

The paradox is still not fully understood, and at this point would not form the basis for a therapy, as lead is toxic for the nervous system.

But scientists have claimed that the phenomenon may lead to promising alternative approaches to the gene therapies that are now a focus of study.

"We know that environmental exposure to lead is a risk factor for ALS. That's why it's so surprising that, according to studies done with laboratory animals, higher levels of lead appear to significantly reduce motor neuron loss and progression of ALS," said Dr. Joseph Beckman.

He said that research would continue to explore the underlying mechanisms that may be causing this.

Beckman said that lead appears to have some interaction with astrocytes, a special type of cell that is believed to influence the spread of ALS.

Astrocytes are a major component of brain cells and, in healthy systems, help to support neurons, defend them against infection and injury and remove neurons when they become damaged.

This delicate process, however, may get disrupted in ALS, at which point astrocytes are believed to play a role in causing inappropriate motor neuron death.

"These systems are very carefully balanced and many factors have to work together. The proper functioning of astrocytes is essential to life, but their dysfunction may lead to disease. We think that lead somehow is modulating the neuroinflammatory actions of astrocytes and, in the case of ALS, helping to shift their balance back to one of protection, rather than damage," said Beckman.

At this time, according to researchers, it appears that astrocytes can stimulate the production of "vascular endothelial growth factor," which in turn protects motor neurons.

The researchers have said that more research is necessary to determine the mechanisms by which lead has this protective effect, which may help to identify pharmacological targets for the disease.

They pinpointed that the levels of lead that were therapeutic in the mice have toxic risk in adult humans.

However, as more is learned about how lead is affecting ALS, alternatives to lead might be found to accomplish the same goal.

"Available evidence supports the view that astrocytes are key targets of lead and respond to it by inducing neuroprotective pathways. Our results suggest that lead activates a novel pathway able to reduce neuroinflammation and slow neurodegeneration in ALS," wrote the researchers in their report.

The research was published in Neurobiology of Disease. (ANI)

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