A new drug to combat Parkinson's disease is surprisingly effective and may cause fewer side effects than similar drugs currently on the market. Patients treated with pramipexole dihydrochloride see an average 20-percent reduction in the severity of their symptoms, according to the first large-scale study of the drug's effects on patients in the early stages of Parkinson's disease.
The drug was approved last week by the Food and Drug Administration and will be available in pharmacies around the nation beginning next week under the brand name Mirapex, developed by Pharmacia & Upjohn and Boehringer Ingelheim Pharmaceuticals Inc.
The study of pramipexole dihydrochloride's effects on patients at 20 hospitals around the nation, led by researchers at the University of Rochester, is published in the July 9 Journal of the American Medical Association.
"Pramipexole dihydrochloride is the first of the next generation of an established class of anti-Parkinson's drugs to be launched," says the study's medical director, Karl Kieburtz, M.D., associate professor of neurology at Rochester's School of Medicine and Dentistry. "It appears to be more powerful and to be better tolerated by patients than other such drugs."
About one million adults in North America are afflicted by Parkinson's disease, in which several hundred thousand cells in a tiny region of the brain die for unknown reasons. This pea-sized part of the brain produces dopamine, a neurotransmitter that's key to the control of movement. Parkinson's, which afflicts adults ranging from ages 40 to 80, results in uncontrollable tremors and shaky, stiff, and slow movements. The condition of patients slowly declines over a period of years or even decades, with the hardest-hit unable even to stand or walk. Current drugs reduce the symptoms, but their effects wane with time.
Pramipexole dihydrochloride is a member of a family of drugs known as dopamine agonists, which mimic dopamine and stimulate brain cells just as the natural neurotransmitter would. Dopamine agonists on the market today include bromocriptene (brand name Parlodel) and pergolide (Permax). Doctors use the drugs to alleviate symptoms and also to smooth out the highs and lows of motor control that many Parkinson's sufferers experience while on levodopa (Sinemet), the most powerful anti-Parkinson's drug now available. Adding a powerful new stablemate to the range of drugs already available will improve doctors' ability to find the best mix for each individual patient, Dr. Kieburtz says.
The drug appears to be more effective than other dopamine agonists in reducing tremors and movement problems. In addition, unlike current drugs, pramipexole dihydrochloride does not cause lightheadedness resulting from a noticeable drop in blood pressure when a patient stands up. Dr. Kieburtz says that's probably because the drug targets the specific dopamine receptor involved in Parkinson's disease more precisely.
"Pramipexole dihydrochloride had a very good tolerability and safety profile," Dr. Kieburtz says. "We thought this drug would be effective, but we were pleasantly surprised that it works so well. I have many patients who have anxiously waited for this drug to become available." Pramipexole dihydrochloride is the first of several next- generation dopamine agonists being launched by pharmaceutical firms this year.
At the study's outset, 264 patients with symptoms of early Parkinson's disease who were not being treated with levodopa were randomly divided into five treatment groups. Members of one group received a placebo, while those in the other four groups received daily doses of pramipexole dihydrochloride. Physicians measured a patient's condition by monitoring the patient's mood, motor skills, and ability to perform everyday tasks. Over the 10-week study, patients receiving pramipexole dihydrochloride improved an average of 20 percent compared to patients taking a placebo. "Patients with worse symptoms saw even bigger gains, suggesting that the drug may be useful in treating mild to moderate cases of Parkinson's disease," Dr. Kieburtz says.
Physicians have begun a two-year study of 300 patients funded by Pharmacia & Upjohn and led by the University of Rochester to study the long-term effects of the drug.
The research was supported by Pharmacia & Upjohn, which supplied the drug, as well as the National Institutes of Health and the National Parkinson Foundation. Dr. Kieburtz's collaborators in the study included Ira Shoulson, M.D., and Michael McDermott, Ph.D., at the University of Rochester, Stanley Fahn, M.D., of Columbia University, Anthony Lang, M.D., of The Toronto Hospital, Warren Olanow, M.D., of Mt. Sinai Hospital, John Penney, M.D., of Massachusetts General Hospital, and G. Frederick Wooten, M.D., of the University of Virginia Health Sciences Center.
At Rochester the study was coordinated through the Department of Neurology's Clinical Trials Coordination Center and the Division of Experimental Therapeutics, where physicians are trained to design and interpret studies of potential new treatments to neurodegenerative diseases.