para-AminoSalicylic Acid may cure Parkinson's-like illness

Researchers have discovered that a drug used to treat tuberculosis apparently cures patients of a Parkinson's-like illness suffered by thousands of mineworkers, welders and others exposed to high levels of the metal manganese.

Manganese is used to produce steel alloys and as a coating on welding rods, among other industrial applications. It replaced lead decades ago as a component in unleaded gasoline, increasing the risks of manganese intoxication for the general public, said one of the researchers, Wei Zheng, at the Purdue University.

When manganese builds up in toxic levels in the body, people suffer from "occupational manganese parkinsonism," which causes symptoms similar to Parkinson's disease. Victims experience hand tremors, poor coordination, unsteady gait and a masklike inability to show facial expressions.

Manganese contained in the coating of welding rods is released in fumes. Welders involved in manufacturing vehicles, tanks and ships are especially prone to manganese intoxication because they work in close quarters, increasing their exposure to the metal.

" There are about 430,000 welders in the United States alone, and even more in China, so manganese intoxication likely affects many people, including workers involved in manganese mining and steel production," he said. " In Beijing, we found a high percentage of welders have these symptoms."

While the condition's symptoms are similar to those of Parkinson's disease, the standard treatments for Parkinson's disease, including the drug Levodopa, are not effective for manganese intoxication.

A chemical compound called EDTA has been used to help patients eliminate manganese in the urine. The drug's effectiveness, however, is limited because it is water-soluble, preventing it from readily passing through membranes in the "blood-brain barrier.

Ten researchers from institutions around the world - including Purdue - conducted a 17-year medical follow-up study on a manganese-poisoned worker and about 80 other patients. The researchers learned that an Aspirin-like drug called sodium para-AminoSalicylic Acid, or PAS, dramatically reduces symptoms on a long-term basis.

" The amazing thing is that this drug reverses Parkinson-type symptoms of manganese intoxication," Zheng said. " We see remarkable improvement after treatment with this drug even 17 years later."

PAS has been used for decades to treat tuberculosis and apparently can cross the blood-brain barrier because it is lipophilic.

The findings are published in the Journal of Occupational Environmental Medicine.

The research has focused on China because that country is a major manganese ore producer and provides one-third of the world's supply of steel alloys.

The paper includes data from research involving a female Chinese mineworker who suffered debilitating symptoms, including lack of coordination, trouble walking and writing, and a masklike appearance caused by tense facial muscles. The woman's symptoms nearly disappeared after treatment with PAS in 1987, and she remained free of symptoms when re-examined during a follow-up study in 2004.

The researchers suggest several possible mechanisms that enable the drug to reverse symptoms of the illness. One is that the drug may contain "chelating arms" that grab manganese.

" However, we are not just looking at this drug as a chelating compound, but also as an anti-inflammatory, like Aspirin," Zheng said. " Historically, we have believed that neurodegeneration is permanent and cannot be reversed, but PAS appears to shed light on a reversal mechanism.

Source: Purdue University, 2006