Source: Harvard Gazette
Date: 24 February 2005

New drug eases effects of Parkinson's disease

Helps those in moderate, advanced stages of disease

By William J. Cromie
Harvard News Office

A successful test of a new drug indicates that it can improve life for those with moderate and advanced Parkinson's disease. Called rasagiline, the medication promises to reduce the time when other drugs are least effective and symptoms of tremors, stiffness, and impaired movement are at their worst, researchers report.

"It made life easier and more predictable for patients who took it over a six-month trial period," says David Standaert, an associate professor of neurology at Harvard Medical School. "Instead of taking other drugs several times a day, rasagiline can be taken only once in the morning."

Many Parkinson's patients take levodopa, usually the first drug given when symptoms begin to impair movement. But levodopa's beneficial effects often wear off. Sufferers gradually experience more and more "off'" times, when the drug is least effective. When hundreds of such patients living in 57 different places in the United States and Canada took rasagiline, their bad times decreased significantly.

"Patients in our study who were taking levodopa experienced at least two and a half hours of 'off' time a day," Standaert notes. "We saw a net reduction in that time of about one hour with a higher dose of rasagiline. A lower dose provided an extra half-hour of 'on' time."

Another study published in 2002 showed that rasagiline helps patients in the early stages of Parkinson's who do not take levodopa. "Now we have found that those with more advanced disease can also get significant relief," Standaert adds.

The new research results were reported in the February issue of the Archives of Neurology. Not included in this report is some preliminary evidence that rasagiline may slow the inexorable progress of this incurable disease. "We see some signs that the longer people take rasagiline, the slower their disease progresses," Standaert says. "It's an intriguing finding, but we can make no claims until we get more proof."

Getting more 'on' time

The latest published study was done by the Parkinson Study Group, an independent, nonprofit team of investigators based at various medical centers in the United States and Canada. It conducts trials of experimental Parkinson's drugs and has helped bring five of them to market. Based on their work with rasagiline, a new drug application has been filed with the U.S. Food and Drug Administration and with comparable agencies in Canada and Europe.

"The FDA is likely to approve it very soon," notes Standaert, who works at Massachusetts General Hospital in Boston, one of the medical centers in the Parkinson Study Group.

An estimated 1 million Americans have the disease, with some 50,000 new cases occurring in the United States every year. It usually attacks people older than 50 years, and men are more likely to be affected than women. More than half of these patients suffer from moderate to advanced forms of Parkinson's.

No one knows what causes the disease beyond the fact that it involves a loss of dopamine, a chemical needed for transmitting nerve impulses between brain cells that control movement. That loss causes trembling of the hands, a shuffling gait, shaking of the head, and a rigid stoop, symptoms clearly visible in Pope John Paul II. Eating, washing, dressing, and other everyday activities gradually become difficult to manage; speech may slow, and patients commonly become depressed.

The body converts levodopa and other drugs to dopamine to reduce such symptoms, but these medications cannot eliminate them. Everything worsens during the dreaded "off" times.

"Rasagiline works in a different way," Standaert points out. "It blocks the breakdown of dopamine in the brain. Instead of replacing it, it makes the most of what's there."

The new drug was well tolerated, say the investigators, although a small number of patients lost weight and appetite, experienced vomiting, and had balance difficulties. Such side effects are considered minor. On the plus side, fewer patients reported depression.

"Rasagiline not only significantly improved patients' ability to perform activities of daily living in the 'off' state, it also improved motor function in the 'on' state," notes Matthew Stern, a professor of neurology at the University of Pennsylvania, one of the principal investigators for the study.

"It needs to be taken only once a day, whereas many patients take levodopa and other drugs several times a day," Standaert adds. "It works in both early and advanced stages of the disease. Therefore, it has the potential to be a promising new treatment for Parkinson's disease. If further research shows that rasagiline slows the progress of Parkinson's, it's potential will be even greater."
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