A pair of ultra-thin electrodes surgically implanted deep into the brain might slow the progression of Parkinson’s disease, according to five-year outcomes from a 30-patient randomized clinical trial conducted by investigators at Vanderbilt University Medical Center.
Their report, published in the July 2020, issue of Neurology, presents the latest findings from the world’s first study of deep brain stimulation, or DBS, for early stage Parkinson’s, defined as within four years of disease onset.
Parkinson’s is a long-term neurodegenerative disorder most obviously characterized by tremor, rigidity, slow movement (bradykinesia) and difficulty with balance and walking. As of 2016, some 6.2 million people worldwide were living with Parkinson’s. According to the Parkinson’s Foundation, as many as 60,000 Americans are diagnosed each year with the disease.
From 2006 to 2009, the investigators enrolled 30 patients, all of whom received optimum drug therapy, with a random half additionally receiving DBS, which is often characterized as a pacemaker for the brain. In the DBS group, electrodes were positioned through two surgical openings in the cranium to deliver electric pulses to the subthalamic nucleus, a small cluster of neurons located deep within the brain on both sides. As with a heart pacemaker, the electric pulses are supplied by a battery implanted under the skin near the collarbone.
After five years, compared to patients who received early DBS in addition to drug therapy, “the patients in our study who received optimal drug therapy alone had fivefold greater odds of experiencing worsening of their rest tremor, a hallmark of this disease,” said senior author David Charles, MD, professor and vice-chair of Neurology.
The FDA has approved VUMC to lead a 130-patient, multi-site double-blinded randomized clinical trial of DBS for early stage Parkinson’s. If results of the pilot trial are replicated in that larger study, DBS will become the first therapy proven to slow the progression of any element of Parkinson’s.
“Parkinson’s is relentless,” Charles said. “There’s nothing that slows down its progression. With this pilot study, we’ve shown that if DBS is implanted early it’s likely to decrease the risk of progression, and if this is borne out in our larger study it would be a landmark achievement in the field of Parkinson’s disease.”
In other five-year outcomes from the study, the DBS patients required considerably less of the medication used to manage symptoms of Parkinson’s.
Also, “Patients receiving only optimal drug therapy had fifteenfold greater odds of needing multiple types of Parkinson’s disease medications,” said project leader Mallory Hacker, PhD, MSCI, assistant professor of Neurology.
In a marked but uncertain trend falling just short of statistical significance, Parkinson’s patients receiving drugs alone were more than twice as likely to have clinically significant worsening of their motor symptoms.
“What this pilot study is most clearly telling us is that the new FDA approved Phase III study must be done to definitively determine whether DBS slows the progress of Parkinson’s disease when implanted in the very earliest stages,” Charles said.
“While this is an incredibly exciting finding, patients and physicians should not change clinical practice at this time.”
Hacker and Charles were joined by Peter Konrad, MD, PhD, nine other investigators from VUMC, and one investigator from Walter Reed National Military Center.
The study was funded by the National Institutes of Health (TR000445, EB006136), the Michael J. Fox Foundation for Parkinson’s Research, and Medtronic, Inc., the manufacturer of the DBS system.
