MIAMI—New methods to combat Parkinson’s disease were described at the Seventh International Congress of Parkinson’s Disease and Movement Disorders—including new drug therapies and new ways to use old ones. Promise was shown in the transdermal delivery of a dopamine agonist and also in clinical studies involving chronic glial growth factor infusions administered directly into the putamen for the treatment of advanced Parkinson’s disease. Deep brain implantation continued to be of interest.

Despite the development of new drugs, there was general agreement that the gold standard remains levodopa. So it was of interest that the final results of the ELLDOPA trial (Earlier versus Later Levodopa), presented by Stanley Fahn, MD, showed that whether the drug was initiated early or late in the course of illness, there was no difference in disease progression.

Dr. Fahn, who is the H. Houston Merritt Professor of Neurology and Director of the Center for Parkinson’s Disease and Other Movement Disorders at Columbia University in New York City, reported a study of 360 drug-naive patients with early disease. Patients were randomized to one of three dosages of levodopa (150, 300, or 600 mg/d), or placebo, for 40 weeks, followed by a two- or four-week washout period.

“This study failed to find any evidence that early levodopa treatment is harmful, or hastens progression of disease,” Dr. Fahn said. Despite the findings, he had some reservations about the study. The two-week washout period may not have been long enough, and there was also disagreement between the results by CIT-SPECT imaging, which was performed in a subset of patients, and the clinical results shown. Nevertheless, he said, “Current methods of customizing the dose to the patient continue to be a reasonable approach.”

TRANSPLANT STUDY DISAPPOINTS

There was one disappointment among the results presented—the second double-blind fetal transplant trial in which 34 patients received either one or four fetal transplants bilaterally, or a sham transplant. It was shown that the transplants did not improve disability scores in the patients, and in some cases actually worked too well, supplying excess dopamine that caused disabling dyskinesias, which in three patients required surgical intervention.

C. Warren Olanow, MD, of the Department of Neurology at Mount Sinai School of Medicine in New York City, commented that despite improvements in fluorodopa uptake seen on positron emission tomography scans in some of the 31 patients who completed the trial, the clinical results were a disappointment. He noted that treated patients’ Unified Parkinson’s Disease Rating Scale (UPDRS) scores improved for about nine months, and then worsened. He added that treated patients who had lower UPDRS scores at baseline did improve significantly more than those on placebo, while those with higher scores did not significantly improve. Also, 13 of 23 treated patients developed disabling dyskinesias off medication, while none of the placebo patients did.

The disappointment in these results was compounded because of a trial reported last year by Curt R. Freed, MD, Head of the Division of Pharmacology and Toxicology at the University of Colorado School of Medicine, which involved 40 patients with advanced Parkinson’s disease who were randomized to either transplants or sham surgery. That study showed that 15% of patients had dyskinesias even after discontinuing all levodopa. Unlike the Olanow study, the trial by Dr. Freed and colleagues demonstrated that motor symptoms improved in the transplant group as a whole, with the response directly related to the preoperative response to levodopa.

NR

—Jean McCann

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