HILTON HEAD, SC—An expanded indication for deep brain stimulation (DBS) in mid-stage Parkinson’s disease, approved by the FDA in November 2015, is “a big step” toward use of DBS earlier in the disease, said David Charles, MD, Professor and Vice-Chair of Neurology at Vanderbilt University in Nashville and Chief Medical Officer of the Vanderbilt Neuroscience Institute.
David Charles, MD
Results from a pilot trial of DBS in early Parkinson’s disease suggest that early treatment may slow the progression of tremor, a finding discovered by Mallory Hacker, PhD, Assistant Professor of Neurology at Vanderbilt University. “If this finding holds up in a pivotal trial, this would be the first therapy shown to slow the progression of anything in Parkinson’s disease,” Dr. Charles said.
Expanded Indication
Since 2002, DBS has been indicated for advanced Parkinson’s disease when symptoms are no longer adequately controlled with medicine. This year, Dublin-based Medtronic announced that the FDA had approved an expanded indication for its DBS therapy. Bilateral stimulation of the subthalamic nucleus or internal globus pallidus gained an indication for adjunctive therapy in patients with Parkinson’s disease duration of at least four years and at least four months of motor complications.
This expanded indication was based on results from the EARLYSTIM clinical trial published in the New England Journal of Medicine in 2013. The trial enrolled 251 participants with disease duration of at least four years and the presence of dyskinesias or other motor fluctuations. Patients treated with DBS and medical therapy reported an average 26% improvement in disease-related quality of life at two years, compared with a 1% decline in patients treated with medical therapy alone.
Researchers have hypothesized that early treatment with DBS might slow the progression of Parkinson’s disease, and preclinical studies suggest a possible mechanism by which DBS could have this effect, said Dr. Charles. Caryl Sortwell, PhD, Professor of Translational Science and Molecular Medicine at Michigan State University in Grand Rapids, and colleagues have shown in animal models that brain-derived neurotrophic growth factor (BDNF) is upregulated in the substantia nigra when the subthalamic nucleus undergoes stimulation. This increased production of BDNF may be therapeutic and also neuroprotective, Dr. Charles said.
Four Patients in Pilot Study Improved
In 2006, researchers at Vanderbilt University initiated a pilot study in 30 patients with early Parkinson’s disease to evaluate the safety and tolerability of DBS. Participants were between the ages of 50 and 75, had received medication for at least six months but not more than four years, and had no history of dyskinesias or other motor fluctuations. Participants had an average age of 60 and had been on medication for an average of about two years. Half of the participants received DBS plus medicine, and half received standard medication only. They were followed for 24 months. Researchers observed a trend toward better motor outcomes in the DBS group, compared with the medication-only group, but the differences were not statistically significant. In addition, the DBS group took less medication than the medication-only group at every time point. At two years, the medication-only group began to experience complications of therapy (eg, fluctuations or dyskinesias), whereas the DBS group did not.
Every six months during the study, patients were admitted to the hospital and stopped all medicine (and stimulation, if present) for a week. Motor scores after the washout periods in the DBS group trended better than those in the medicine group at 24 months. When researchers evaluated patients’ motor scores after each washout period individually, all 14 patients in the medication-only group worsened over two years. In the DBS group, five of 14 patients did not worsen; four patients actually improved. “That should not happen,” Dr. Charles said. These results from the pilot study suggest “a nearly fourfold increase in the chance of not worsening if you give DBS plus medicine early,” he said.
In addition, when researchers examined patients’ tremor after the seven-day washout, tremor scores in the DBS group did not worsen, whereas tremor scores in patients who received medication only slowly worsened over time as expected.
