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New Drug Prolongs Symptom Relief in Parkinson's Disease

For release: Thursday, April 29, 1993

A new drug, when added to standard treatment for Parkinson's disease, prolongs relief of symptoms by more than 60 percent, report scientists from the National Institute of Neurological Disorders and Stroke (NINDS). In announcing their findings today at the annual meeting of the American Academy of Neurology in New York,* scientists said that the drug, called R0 40-7592, could help overcome drawbacks of current drug treatment.

"Although the current drugs are very effective in the short run, nearly half of treated Parkinson's disease patients develop complications after five to six years," said Thomas Chase, M.D., who is chief of the NINDS experimental therapeutics branch and has been testing drug treatments for Parkinson's disease for more than 20 years. "These findings offer hope that we can improve our track record in treating Parkinson's symptoms."

More than half a million Americans have Parkinson's disease, a neurological disorder of later life that progressively impairs control of body movement, interferes with such abilities as walking and talking and often leads, over time, to rigid immobility. Although standard treatment with the drug combination drug levodopa/carbidopa can restore virtually normal movement early in the disease's course, the treatment loses effectiveness as the disease progresses.

For example, many patients develop the so-called wearing-off phenomenon, in which the length of time that patients benefit from each dose of levodopa/carbidopa progressively shortens. In some cases, a single dose that would have originally restored movement for as long as 4 to 6 hours may only last for 2 hours.

"The wearing-off phenomenon can be tremendously disabling to patients and represents a significant challenge to physicians who treat them," Dr. Chase said. "As the window of benefit grows smaller and smaller, many patients develop prolonged periods of severe impairment that force them to stop working or participating in other activities."

In the double-blind placebo-controlled study, NINDS scientists administered standard levodopa/carbidopa doses to 10 patients, supplementing each day's first dose with Ro 40-7592 or with a placebo. Scientists them measured motor function after treatment. When patients were treated with levodopa/carbidopa and 100 mg of Ro 40-7592, their periods of improved movement lasted an average of 69 percent longer, rising from 78 minutes, with levodopa/carbidopa alone, to 132 minutes. Scientists said additional research is needed to learn whether multiple daily doses of the experimental drug can provide even further improvement.

"This treatment shows promise because it addresses a serious problem faced by patients with Parkinson's disease," said John W. Roberts, M.D., the NINDS neurologist who led the study. "This drug makes the same amount of levodopa/carbidopa last longer. Normally patients must take more doses and increasing amounts of levodopa/carbidopa as the disease progresses so that they can maintain a constant level of relief from symptoms. As a result, the treatment becomes very inconvenient and patients experience increasingly severe side effects."

Ro 40-7592 belongs to a class of drugs known as catechol-O-methyltransferase (COMT) inhibitors, which block the breakdown of dopamine and levodopa (the chemical precursor of dopamine). Parkinson's disease patients have a shortage of the neurotransmitter dopamine, which functions as a chemical messenger between nerves. This shortage disrupts brain messages that control body movement thus causing the disease's symptoms. "This class of drugs offers a promising strategy for improving Parkinson's disease treatment," said Dr. Roberts. "Since we can slow the breakdown of levodopa and dopamine, we can now help patients avoid some of the problems of the wearing-off effect while taking fewer doses and smaller amounts of levodopa/carbidopa."

In a second study of this approach to treating Parkinson's disease, NINDS grantees led by Dr. John G. Nutt at the Oregon Health Sciences University in Portland today announced results with another COMT inhibitor, the drug encapatone.** In this study, patients were given the drug with each dose of levodopa, and scientists observed a 50 percent increase in the number of hours with improved motor performance.

The NINDS, one of the 16 National Institutes of Health in Bethesda, MD, is the primary supporter of brain and nervous system research in the United States and a lead agency for the Congressionally designated Decade of the Brain.

*Presenter: Dr. John W. Roberts, NINDS
Paper Title: "Cathechol-O-Methyltransferase Inhibitor Ro 40-7592 Prolongs Duration of Action of Levodopa/Carbidopa in Parkinsonian Patients."
Paper Number; 684S
Time/Location of Presentation: Thursday, April 29, 9:30 a.m., Grand Ballroom East

**Presenter: Dr. John G. Nutt, NINDS Grantee, Oregon Health Sciences University in Portland"
Paper Title: "Effect of an Inhibitor of Catechol-O-Methyltransferase (COMT) on the Pharmacokinetics and Pharmacodynamics of Levodopa."
Paper Number: 682S
Time/Location of Presentation: Thursday, April 29, 9:00 a.m., Grand Ballroom East

Last Modified August 7, 2009