Using a new kind of clinical trial, researchers may have discovered the first drug that can actually delay the progression of Parkinson's disease, a disabling and ultimately fatal neurological disorder. Several drugs are available that can mitigate the symptoms of Parkinson's, but that very easing of the symptoms makes it extremely difficult to tell whether the drug is having any permanent effect on the disease itself. To get around that problem, Dr. C. Warren Olanow of the Mount Sinai School of Medicine in New York and his colleagues used an unusual clinical trial design called a delayed-start trial. The idea of the trial is to start two groups of patients on a drug at different times. If the drug is actually delaying the progression of the disease, then the group that gets it later should not receive as great a benefit as those who received it first.
Olanow and his colleagues at 129 medical centers in 14 countries studied 1,176 patients with early Parkinson's disease who had not been given other forms of therapy. Half the patients were given the drug rasagiline (sold under the brand name Azilect by Teva Pharmaceutical Industries of Israel) and half a placebo. After nine months, the group that had been given placebo was also given rasagiline, while those who had received it initially continued to receive it. The progression of their disease was measured on the widely used Unified Parkinson's Disease Rating Scale, which ranges from zero to 176 and includes subscales of mental function, activities of daily living and motor events. Higher scores indicate more severe disease.
The team reported today in the New England Journal of Medicine that patients given a 1-milligram dose of the drug for the entire 18 months of the study showed less worsening of the disease in the first nine months. Their symptoms were improved as much as those in the second group during the second nine months of the study. In short, they were better off at the end of 18 months than the patients who had received Azilect for only nine months, suggesting that the drug had delayed the course of the disease. "If this can be confirmed, this would be the first drug determined to have a disease-modifying effect in Parkinson's disease, and that is exciting news for the PD community," Olanow said.
But Olanow noted a complication of the study: Those who received a 2-milligram dose of the drug were, overall, no better after 18 months than those who had received the higher dose for only nine months. He speculated that the reduction of symptoms from the higher dose made it difficult to observe any effects on disease progression. This possibility was supported by the observation in a small group with the most serious symptoms that they did do better after 18 months, but it will require further study.
Parkinson's disease affects more than 1 million Americans and is characterized by impaired motor skills including tremor, stiffness and slowness of movement. The symptoms worsen as the disease progresses. The most common treatment is the drug levo-dopa, which replenishes a neurotransmitter that is lost in the course of the disease. Because Azilect has few side effects and only modest benefit for symptoms, Olanow suggested that it would be best to use it early in the course of the disease and save other drugs for when symptoms worsen.
The study was funded by Teva, which was responsible for data collection, monitoring and statistical analysis. Olanow reported receiving consulting and lecture fees from the company.
-- Thomas H. Maugh II
Photo: Pope John Paul II was one of the many victims of Parkinson's disease. Credit: Vincenzo Pinto / AFP