A new drug under trial at the University of Alabama at Birmingham (UAB) promises to be effective in reducing tremors, muscle rigidity and other debilitating symptoms that mark the onset and progression of Parkinson's disease. Results of the study, led by a team at UAB, were published January 3 in the online edition of Neurology.
Rotigotine is a dopamine agonist that mimics the action of dopamine in the brain and compensates for the shortage in patients whose dopamine brain cells have been damaged by disease. The study followed 302 patients with early-stage Parkinson's disease at 50 clinical sites throughout the United States and Canada. Patient symptoms were measured using the Unified Parkinson Disease Rating Scale (UPDRS) that measure the degree of disability following six months of therapy with rotigotine or a placebo. The group receiving rotigotine showed a significant decrease in their UPDRS scores, which indicates an improvement of symptoms. The placebo group had a continued increase in UPDRS, indicating worsening symptoms.
A key finding of the study is the effectiveness of the transdermal patch, the delivery mechanism used in administering the rotigotine. "It allows the medication to be absorbed through the skin at an even rate over 24 hours," said Dr. Ray Watts, chair of the UAB Department of Neurology and principal investigator of the study. "Since the responsiveness of shorter-acting drugs now used to treat Parkinson's disease becomes more variable as the disease progresses over time, the transdermal patch may have advantages because of the continuous delivery of the therapy, which avoids the abrupt 'off' state that can occur with other therapies."
Gastrointestinal side effects, such as nausea, are also reduced because the medication bypasses the stomach and intestines when delivered transdermally, Watts said.
Rotigotine is also being studied in combination with L-dopa in patients with more advanced disease. "This collection of studies will provide data that supports the use of transdermal rotigotine in early Parkinson's disease patients and those with more advanced Parkinson's disease who are already taking other medications," Watts said. "The nature of Parkinson's disease is to slowly progress over time. The big challenge over 10, 15, 20 years is to continue to get benefit from the medications and limit the side effects because more medication will be needed over time. It is hoped that this new delivery system will improve the long-term outcome."
Parkinson's disease has multiple causes including five genetic abnormalities that have been identified. Those, however, account for less than 10 percent of all patients, according to Watts. Most cases are sporadic and may result from exposure to toxins that affect dopamine cells. Preliminary findings by researchers at the University of North Carolina show that patients with low levels of LDL cholesterol seem to be at greater risk of developing Parkinson's disease than those with higher LDL levels. The study, which targeted 124 patients, indicates a link between Parkinson's disease and the use of statin drugs for lowering cholesterol, according to a January 15 article in Times Online. The findings have prompted additional research, including a large-scale study by Harvard University.
While results of the multicenter rotigotine study are encouraging, Watts is quick to emphasize that a cure for Parkinson's disease has not yet been found. "There's still a need for research to find medicines that not only treat the symptoms, but also slow or stop the underlying progression," he said.
Research is underway to develop neuroprotective therapies, which would possibly eliminate the disease. "We are pursuing research in our labs at UAB that is elucidating the mechanisms that lead to the death of these dopamine cells. As we understand the mechanisms, we can devise targeted, rational new treatments. If we use them early and possibly even before symptoms emerge, then those will be potential cures," Watts said.
Meanwhile, rotigotine, which is manufactured by Schwarz Pharma, is currently under review by the United States Food and Drug Administration and is expected to be approved for general use sometime this year, possibly as early as summer. That's good news for the 4 million people worldwide, including 1 million Americans, who suffer from the central nervous system disorder.
February 2007
