Parkinson's gains cited, but no cure soon

Environmental and genetic triggers are research targets while surgery and neuroprotective drugs slow the disease's relentless progress.

By Susan J. Landers — Posted Oct. 17, 2005

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Washington -- Parkinson's disease is finally beginning to yield some of its secrets to persistent researchers.

"Progress has been flowering in the last few years," said Mel B. Feany, MD, PhD, assistant professor of pathology at Harvard Medical School in Boston.

"There is a world of difference between what we know about Parkinson's disease now and what we knew even five years ago," said Jose Garcia-Pedrosa, chief operating officer of the National Parkinson Foundation.

As the second most common neurodegenerative disease in the United States -- Alzheimer's disease holds the top spot -- Parkinson's disease affects about a million people.

Since Parkinson's is a disease of primarily older people, those numbers are likely to begin climbing as the population ages, said Dr. Feany at a Sept. 21 Capitol Hill briefing sponsored by the Congressional Biomedical Research Caucus.

The disease runs a lengthy course as increasing numbers of the brain's dopamine-producing neurons die. Its symptoms grow progressively worse over 20 years or more, moving from, for example, mild tremors to the inability to stand or walk.

A key goal of research is to determine why these neurons die, Dr. Feany said.

Although there have been major gains in understanding the disease, "the cause and cure have eluded us," Garcia-Pedrosa said in a separate interview. "People like to say we'll discover them in 10 years, but I think that expresses a hope more than a scientifically based reality."

Advocates note that while estimates of medical costs from the disease range into the billions of dollars, federal research funding hovers at about $300 million each year.

Included among the gains made in recent years: Genetic research has offered new insights into the development and progression of the disease, additional environmental risk factors have been identified and new animal models developed, Dr. Feany noted.

"The miracle of deep brain stimulation has been phenomenal, and while we don't understand how it works, it does work," Garcia-Pedrosa said of the surgical procedure in which a battery-operated device similar to a pacemaker is implanted in the brain.

Progress also is being made with neuroprotective drugs that can halt the disease's destruction, he added.

Genome mappings

The first large-scale whole genome map of genetic variability associated with Parkinson's disease was unveiled in early September by researchers from the Mayo Clinic and Perlegen Sciences, a Mountain View, Calif.-based drug development company with a focus on genetics. Their findings highlight changes in 12 genes that could increase the risk for Parkinson's disease.

"This represents one of the first large-scale whole genome association studies of any disease," said lead investigator Demetrius Maraganore, MD, a Mayo Clinic neurologist. "If confirmed, the findings may lead to new insights about the causes of Parkinson's disease."

Although the study found 12 potential susceptibility genes, it found no strong single genetic determinant of Parkinson's disease.

Only during the past decade have researchers discovered that an inherited form of the disease even existed. And this determination has led to an explosion of research into the function of the proteins that are encoded by these genes.

Using this information, researchers have been able to paint a picture of what goes wrong in the brains of people with Parkinson's disease, Dr. Feany said. And the picture isn't pretty. Key are clumps of accumulating protein called Lewy bodies that become poisonous to cells. She compared the clumps to mounds of garbage building during a New York City trash collectors' strike.

Environmental factors long have been suspected of playing a large role in the disease, and a recent study found evidence that loss of a particular gene known to be linked to inherited Parkinson's disease leads to a sensitivity to the herbicide paraquat and the insecticide rotenone.

Rural living has been designated a risk factor for the disease, probably because of heightened exposure to pesticides, Dr. Feany said.

Surprisingly, cigarette smoking has been found to offer protection, as has caffeine. While researchers aren't urging people to take up smoking, increased caffeine intake may warrant a closer look , she added.

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Neuroprotection in Parkinson's

A wealth of new information about how neurons may be damaged in Parkinson's disease has allowed researchers to identify potential ways of treating the disease.

Among these methods are nerve growth factors, anti-inflammatory drugs and antioxidants.

To narrow down the possibilities to the most promising, a committee sponsored by the National Institute of Neurological Disorders and Stroke selected in 2002 four of the most promising drugs for study.

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External links

National Institute of Neurological Disorders and Stroke on Parkinson's disease (link)

American Parkinson Disease Assn. (link)

Parkinson's Disease Foundation (link)

National Parkinson Foundation (link)

Michael J. Fox Foundation for Parkinson's Research (link)

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