Peter Konrad, MD, presents exciting findings that show Deep Brain Stimulation (DBS) of the subthalamic nucleus (STN) in early stage Parkinson’s Disease may slow tremor progress at the Congress of Neurological Surgeon’s (CNS) 2018 Annual Meeting, on Wednesday, October 10, in the General Scientific Session.
“DBS is the first therapy to show disease modifying effect—it can actually slow down cardinal features of Parkinson’s. There has been no therapy, drug or device that has ever been able to do that,” said Dr. Konrad.
More than one million Americans are living with Parkinson’s disease, a progressive neurodegenerative movement disorder that affects movement. Three main characteristics of PD include tremor, rigidity, and bradykinesia (slowness to move). DBS is currently used to treatment symptoms of mid- to –late-stage Parkinson’s, more often as a rescue remedy when medications start to fail because of the invasive nature of the surgery.
Dr. Konrad, vice chairman of research and innovation, and professor of neurological surgery and biomedical engineering at Vanderbilt University, concluded an FDA approved randomized pilot trial with a team at Vanderbilt University Medical Center that included David Charles, MD, and Mallory Hacker, PhD, among others. The landmark clinical trial was limited to 30 patients, aged 50-75 years, with idiopathic PD, to receive optimal drug therapy (ODT), or DBS plus ODT at a series of six-month touchpoints over two years.
One of the reasons this study was important is that DBS has never been used to treat early PD. The investigators wanted to find out if DBS use in early onset patients might affect the course of Parkinson’s, which is characterized by relentless clinical progression of gradually worsening disease characteristics.
Currently, there is no biomarker for disease progression of Parkinson’s. Using a standard benchmark of disease progression for the study, the investigators took patients off their medications for seven days, an extraordinary length of time for any study. Patients were early in the disease so they were able to tolerate the longer time. On the eighth day, the baseline status of their disease was measured by a blinded rater who would measure symptoms and compare it with the best-managed drug group.
The most significant measurement scores were in the area of tremor. Over the course of two years, the patients with DBS + ODT showed almost no worsening of tremor, while patients who were on a course of ODT deteriorated as expected along the disease progression curve. That is to say, patients optimally managed by drugs alone showed significantly worse symptoms of disease progression—three-fold higher (2.6) than in the DBS group. Further, there was a seven-fold odds difference in further worsening of tremor in other areas of the body in the drug-treated only group versus the DBS and drug-treated group.
The investigators plan to review at the same participants at 10 years out of the initial clinical trial. Patient’s will again stay off their medication for an entire week, something basically unheard of in patients treated only by medication ten years into Parkinson’s. This, in itself, tells the researchers that the patients are uniquely doing better.
Up until now, the clinical evidence says nothing can be done to stop the progression of Parkinson’s. This study suggests that DBS of the STN might actually slow down the progression of Parkinson’s, especially with respect to tremor. The implant calms the circuit down with the potential that putting the implant in at the very first sign of Parkinson’s may stop the STN output from being toxic to the brain.
Typically, when a patient is first diagnosed with PD, the disease has already claimed a significant portion of the brain, with a loss of 50–70 percent of neurons. Further, the targeted nature of DBS allows it to be used without the negative side effects that various medications have on the body. And while medication does help control the symptoms, none so far have slowed the disease down.
The FDA has recently granted approval for a 300-patient study at 15 medical centers across the US. The new study will focus on determining if DBS is neuroprotective. The principle investigators are now raising funds for the study and hope to launch it next year. If the study is successful, the FDA would change the labeling of DBS to allow its use in early stage PD. This would revolutionize the treatment of Parkinson’s because patients would get the implant in the early stages and use medication to augment treatment of their disease. DBS could be the best chance to get in front of this degenerative disease affecting so many.