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Fungus May Be a Cause of Parkinson’s Disease : Health: Two researchers say proof will be difficult, but could constitute ‘a major discovery.’

TIMES SCIENCE WRITER

At least some cases of Parkinson’s disease, a devastating neurological illness that affects as many as 500,000 Americans, may be caused by infection by a common soil fungus, researchers from UC Davis will report today.

Infection of laboratory animals with the fungus, called Nocardia asteroides, damages the specific areas of the brain involved in Parkinson’s disease and produces symptoms identical to those found in human patients, the researchers will tell a meeting of the American Society for Microbiology in Anaheim.

“It’s not going to be easy to prove this (that Nocardia causes Parkinson’s in humans), and there are going to be large numbers of skeptics,” said microbiologist Blaine L. Beaman of UC Davis. “It certainly seems unbelievable, but if we can prove it, it translates into a major discovery.”

Pinpointing a cause of Parkinson’s would be of tremendous significance because scientists currently do not know what causes the disease. Furthermore, identifying a cause, particularly an infectious agent, should lead to new ways of preventing the disease, such as immunization against the microorganism.

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Nocardia is widespread in the environment and most people are probably routinely exposed to it, either in the air or through cuts. It normally causes transient flu-like symptoms, such as cough and fever, but it has been observed to cause neurological symptoms in humans, and in some susceptible individuals may actually trigger Parkinson’s, according to Beaman.

Other Parkinson’s researchers were cautious in their assessment of the scientists’ results, primarily because no one had seen the study. But “their finding is intriguing,” said neuroscientist Debra Mash of the National Parkinson’s Foundation. “It fits in with what we already know. There are a lot of things that cause Parkinson’s, and most of us agree that it is something in the environment.”

“That’s an astounding assertion,” said neurologist J. William Langston of the California Parkinson’s Foundation in San Jose, who himself discovered that a contaminant formed in the production of the street drug methamphetamine can cause Parkinson’s. “It would be absolutely fascinating if it is proved to have some basis.”

Parkinson’s disease primarily affects people over 55. Its main symptoms are incapacitating tremors and rigidity of the limbs. As many as 30% of the victims also suffer dementia, a form of mental impairment.

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The disorder results from the death of brain cells that produce the neurotransmitter dopamine, a brain hormone that is particularly important in the control of muscle movement. Symptoms can be alleviated, at least in the early stages, with the drug L-dopa, which is converted into dopamine in the brain.

Physicians are also experimenting with transplanting dopamine-secreting cells into the brains of Parkinson’s victims, but those results, while promising, are still considered inconclusive.

Researchers have never been able to identify the cause of Parkinson’s, however, and that mystery is a source of considerable study. Their best lead in the past was Langston’s discovery that a chemical called MPTP, which contaminates some batches of illicit methamphetamine, causes a Parkinson’s-like disease in young people who use the drug.

At least 400 cases of Parkinson’s disease caused by MPTP are known, and researchers routinely use the chemical to induce Parkinson’s in experimental animals. Many researchers believe that environmental chemicals with a structure similar to MPTP may cause the disease.

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Some pesticides, for example, have similar structures. But no one has ever been able to prove the association.

A report to Congress by the Office of Technology Assessment on Wednesday, in fact, argued that the government is not doing enough to control the release into the environment of chemicals that may have the potential to cause both Parkinson’s and Alzheimer’s disease. The report called for an additional $1.5 million for study of the neurotoxic effects of such chemicals.

Although many researchers have suggested that infections might also be a cause of Parkinson’s, most researchers discount that possibility because of a lack of supporting evidence. No one has ever been able to isolate an infectious agent, such as a virus or bacterium, from the brain of a Parkinson’s victim, and no one has observed any residual traces of the inflammation that would be expected to accompany an infection.

But Beaman and his colleague, microbiologist Shunro Kohbata, who is on sabbatical at Davis from Gifu University in Japan, believe they have found an explanation for the lack of such evidence. “ Nocardia does unique things that other bacteria do not do,” Beaman said.

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When Beaman and Kohbata infused large quantities of Nocardia into the blood of research animals, the animals suffered widespread inflammation and the few that survived showed a variety of neurological symptoms.

But when they infused much smaller doses, they found that the microorganism infected the brain without any inflammatory response--not surprising because immune cells cannot enter the brain unless there is a breach of the blood-brain barrier that shields the brain from potentially toxic chemicals in blood.

In the brain, the Nocardia infection was self-limiting, Beaman said, and it was cleared within two weeks. Only after all traces of the infection were gone did the neurological symptoms develop. “If we didn’t follow the course of events carefully, we would never be able to detect the organism,” he said.

According to Beaman, about 15% of the several hundred animals studied in his experiments developed symptoms that included rigidity on one side of the body (hemiparesis) and head shaking. These symptoms were alleviated with L-dopa. Langston cautioned, however, that hemiparesis is not one of the major symptoms of Parkinson’s, which “raises some doubts” about their discovery.

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Although Nocardia seems to produce no major health effects in most people, it causes a much more serious infection in people whose immune systems are suppressed, such as by AIDS, organ transplants or cancer. In those patients, it can cause serious brain damage or be lethal.

As support for their theory, Beaman and Kohbata noted that many people with severe Nocardia infections have been seen to develop a variety of neurological symptoms, including those of Parkinson’s disease. Even less serious Nocardia infections might trigger such symptoms in genetically susceptible people, they speculated.

Beaman plans to begin looking for traces of Nocardia infection, such as antibodies against it, in Parkinson’s victims, but he acknowledges that a long road lies ahead.

“There may be many etiologies for Parkinson’s. There probably are. Nocardia may be one of them, but it will require a lot of work to find out.”

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