By Leslie Hast
A Vanderbilt University Medical Center study of Parkinson's disease has shown such promise that several other universities have signed on to plan a large-scale, multi-center trial.
The current study, under way since 2006, is testing the application of deep brain stimulation (DBS) in very early-stage Parkinson's disease.
“There is no treatment that has been proven conclusively to slow the progression of Parkinson's disease,” said David Charles, M.D., vice-chair of Neurology and a principle investigator of the study.
“DBS has proven beneficial in the advanced stages of Parkinson's, and we believe that if the therapy were applied very early, it might modify the disease progression and the development of disability.”
Parkinson's disease is a relentlessly progressive motor system disorder, resulting from the loss of dopamine-producing cells, causing tremor, slow movement, stiffness and difficulties with balance and walking.
The DBS device, manufactured by Medtronic, involves a thin wire implanted into an area deep in the brain. The wire runs to a small pulse generator implanted just under the collarbone, similar to a heart pacemaker. Even though the mechanism of action is debated, it is clear that the therapy dramatically improves many patients.
For two years, the researchers are following 30 patients recently diagnosed with early-stage Parkinson's disease, randomized into groups receiving DBS or standard of care, to gather preliminary data necessary for the design of a large-scale trial and to ensure it is well tolerated when applied early in the course of disease.
Wayne Webb, who Charles said had very troubling tremor, was randomized to receive DBS. Webb said the difference the device made in his symptoms was like night and day.
“My right arm shook. It was violent and severe, but now there's nothing. It's drastically different, and most people don't know I have Parkinson's,” he said.
Webb, 60, was diagnosed in early 2005 and found out about the study at a Parkinson's symposium in Memphis. He said he wanted to participate to help future advances in research and felt lucky to be in the group receiving DBS. He has had no negative effects from the device.
“When they take me off my meds and turn off the stimulator, things get ugly. I can't imagine what it would be like to have the constant shaking,” he said.
Charles said this study is unique, but it is only testing the tolerability of the device and gathering preliminary safety information.
“The big question — could DBS modify disease progression — can't be answered until we do a large-scale trial,” he said.
So Charles and his co-investigator, Pete Konrad, MD, PhD, associate professor of Neurosurgery, are embarking on a two-year planning period to prepare for a large-scale study with representatives from Cleveland Clinic, Ohio State University, University of Cincinnati, Rush University, Emory University, University of California-San Francisco, University of Michigan, Stanford University and University of Florida.
The Department of Neurology has pledged $100,000 to the planning effort, and the researchers have submitted a grant application for additional funding from Medtronic, the manufacturer.
“We have been working on this for 10 years, and we need to be planning for the next study right now so we can get started once the pilot is complete,” Charles said. “If we find something in the pilot that indicates we shouldn't proceed, we won't, but the likelihood of that is probably low. If we wait, that is just two years longer that patients have to wait for this answer.”
And time is of the essence in Parkinson's.
“It is estimated that 50 percent of dopamine-producing cells have already degenerated when a patient goes to their physician for the first time with Parkinson's symptoms,” Charles explained.
“So if you want a therapy that would slow the progression, you have to give it as soon as you know the patient has Parkinson's because half of the cells you are trying to save are already gone the day you make the diagnosis.”