Combining clinical expertise and trial design, David Charles, MD, and Mallory Hacker, PhD, MSCI, are ready to undertake a groundbreaking study on treatment for Parkinson’s. (photo by Donn Jones)

Parkinson’s is best known for manifesting with a tremor, but patients may have up to four “cardinal features” that include muscle rigidity, slowing of movements and balance problems.

By: Evan Dorian

Researchers at Vanderbilt University Medical Center have long studied potential therapies to treat Parkinson’s disease, a notoriously devastating neurodegenerative condition. Patients can live with Parkinson’s, but at the cost of being moderately to severely disabled by its effects. 

Parkinson’s is best known for manifesting with a tremor, but patients may have up to four “cardinal features,” notes David Charles, MD, professor and vice chair of Neurology. These cardinal features can include a tremor as well as muscle rigidity, bradykinesia (slowing of voluntary movements) and postural instability (balance problems). 

But patients often find that they suffer from more than just the parts of their disease that are visible to the outside observer. 

“There are unfortunately many non-motor symptoms,” said Charles. “Depression, constipation, anxiety, sleep problems and loss of sense of smell, among others. There’s a laundry list of things that can occur in people with Parkinson’s.” 

Because there is no test to determine if a patient has Parkinson’s, they receive a clinical diagnosis based on their symptoms, findings from a neurologist’s examination and their response to medication. According to Charles, while there is good news on the treatment front, it comes with a stipulation. 

“We’ve got a lot of medications for Parkinson’s, but the bad news is they only help the symptoms for a few hours after you take the tablet. They don’t slow down the underlying degeneration that’s going on in the brain,” said Charles. “So what we’re going for is the first treatment that would slow or stop the motor symptoms from progressing in Parkinson’s disease.” 

Charles and his colleague Mallory Hacker, PhD, MSCI, assistant professor of Neurology, have for years studied deep brain stimulation, or DBS, a treatment that may offer hope for Parkinson’s patients — particularly if the therapy is applied in the earliest stages of the disease. 

Recent findings from Hacker identified that a “sweet spot” deep within the brain has direct lines of communication to motor regions far out on the surface of the brain — the cerebral cortex. Results suggested that stimulation of a specific site in the dorsolateral subthalamic nucleus is associated with both slower motor progression and long-term motor improvements in Parkinson’s disease. 

To further advance their research, Charles and Hacker have received Food and Drug Administration approval to lead a multicenter clinical trial to assess patients’ responses to DBS, which they hope will pave the way for a paradigm shift in treatment of patients with Parkinson’s. 

Despite the complex nature of treating a neurodegenerative disease, Charles and Hacker’s plans for the trial are relatively straightforward: The goal is to enroll 134 patients at up to 20 centers across the country and assess the effectiveness of DBS in slowing or stopping the progression of Parkinson’s disease. 

While all of the participants would be implanted with a DBS electrode, half would have the electrode turned on and half would have it remain off. The study would be double-blind, meaning that neither patients nor research doctors would be aware of who was in which group. 

Hacker explained that, building on a practice from an earlier phase of the research, a unique feature of the planned study is a seven-day therapy “washout,” which allows doctors to measure how effective the patient’s treatment was against their baseline. 

“Patients came in and were evaluated essentially in two states. They were evaluated on their DBS and medications to assess: How are patients living, and how well is the therapy treating their symptoms?” said Hacker. “And then they were asked to stop the medication and have their stimulator turned off, and they were ‘washed out’ of those very potent symptomatic therapies for a week so that we could evaluate their untreated motor symptoms of Parkinson’s.” 

Following the therapy washout and assessment, patients can then be randomly selected to either receive DBS treatment or be part of the group with an inactive electrode. 

“In doing this, we remove the therapy for a week, and that lets us have a really good understanding of how the underlying progression of the disease is evolving over two years when you compare the two groups,” said Hacker. “This is the trial design that we plan to carry forward in the upcoming multicenter Phase 3 clinical trial because it gave us some really interesting data to look at.” 

Credit: VUMC News

Full article: https://news.vumc.org/2025/04/07/vanderbilt-neurology-research-duo-shares-details-of-new-clinical-trial-that-would-take-aim-at-slowing-or-stopping-the-progression-of-parkinsons-disease/

Stimulating Brains Podcast | Episode 57

Mallory Hacker is an Assistant Professor for Neurology in the team of David Charles, who is Professor of Neurology, Vice-Chair for Business Development and Strategy, as well as the Medical Director for Telehealth at Vanderbilt University Medical Center in Nashville, Tennessee. In 2006, after a stay at Alim Louis Benabids team in Grenoble, France, David started to investigate the question of whether subthalamic DBS could lead to slowing of motor progression in patients with early stages of Parkinson’s Disease. In a one-of-a kind trial, he collected data on the first patients which were published in 2014.In subsequent follow up trials, many of which were first-authored by Mallory Hacker, Class II evidence that supports this hypothesis could be established. It was a great joy to host Mallory in my lab in Berlin in 2022 and we have looked at the effects of lead locations on patients enrolled in the pilot trial. This is what convinced me that there might be something: The few patients that did not progress at all in their motor symptoms after two years were all precisely stimulated at the optimal location within the STN, while the ones that did progress, were more off target. Indeed, these same optimally placed patients had lower stimulation amplitudes and received less medication – but still had a clearly better outcome. Since the original trial, David and Mallory have been hard at work in trying to secure funding for a phase III pivotal trial, and we discuss how difficult this process has been, but also, that there is hope on the horizon, regarding the next steps!

A man who has been battling Parkinson’s disease for seven years shared a video on TikTok demonstrating the astounding results that deep brain stimulation has had on his ability to use his hands.

Justin Fields, a 35-year-old Knoxville, Tenn., resident, shared a video on TikTok of himself eating cereal with a spoon with the help of his deep brain stimulator, a device that is surgically implanted in the brain and helps people with Parkinson’s control their moments and tremors.

In the video, which was recorded by Fields’ fiancée Emily Norris, he first demonstrates how his body functions without the stimulator. Fields can clearly be seen struggling to pick up the cereal bowl in front of him and raise the spoon to his mouth to take a bite. But after switching the device back on, Fields is able to eat the cereal with relative ease.

Read more on Yahoo!

Among patients with Parkinson disease (PD) aged 60 years and younger with early motor complications, deep brain stimulation (DBS) was found to provide significant improvements in social, occupational, and psychosocial function, according to study findings published in Movement Disorders Clinical Practice.

As the researchers noted, DBS has been shown to improve motor symptoms and quality of life in patients with PD (PwP) and early motor complications. Moreover, the safety of DBS has been indicated in a prior study, with previous concerns of dementia risk found not to be higher than the general PD population who did not undergo the procedure. The implications of these benefits led researchers of the current study to examine whether DBS could be prescribed in the working-age PD population.

Read more at AJMC

Deep brain stimulation (DBS) can decrease the risk for disease progression as well as the need for and complexity of medications in patients with early-stage Parkinson disease (PD) compared with optimal medical therapy alone, according to study results published in Neurology. Previous studies reported the benefits of DBS in mid- and advanced-stage PD, but there are limited data on the long-term safety and efficacy of DBS in early-stage PD.

Read more at Neurology Advisor

Overview of attention for article published in Neurology, June 2020

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. ….

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.

Read more at VUMC Reporter

Data from a five-year clinical trial is adding to growing evidence that deep brain stimulation (DBS) can slow the ravages of Parkinson's disease.

Researchers at Vanderbilt University Medical Center in Nashville, Tenn., said that the therapy appears to curb any worsening of tremor and other symptoms, as well as lessening a patient's need for medications.

"Parkinson's is relentless," senior study author Dr. David Charles, Vanderbilt professor and vice-chair of neurology, said in a medical center news release. "There's nothing that slows down its progression."

However, "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," he said.

Read more at US News & World Report

For the first time, a treatment for Parkinson’s disease may actually help stop its progression. In new research presented at the Congress of Neurological Surgeons this month, deep brain stimulation (DBS) was shown to have significant beneficial effects when utilized in people earlier than previously believed.

Read more at Healthline

Larry Clift, 74, of Chattanooga, lies on an operating table with a sheet of plastic draped across his forehead, nearly splitting the room in two. On one side, bright lights illuminate a dime-sized hole in the top of Clift’s skull, surrounded by a white ring of exposed bone and a small ooze of blood. If you look closely, you can see his brain….

For eight years, he has suffered from Parkinson’s disease, a disabling condition that has made his body stiff and weak. Relentless tremors have taken over his right arm, and doctors are certain they will spread to his left if they do not intervene. This operation, as surreal and terrifying as it may sound, is supposed to help. During four hours of surgery, a team of doctors place a tiny electrode deep within Clift’s skull, where electric shocks can stimulate the portion of his brain at the root of his disease. If the procedure works, his symptoms will fade with the flip of a switch. And maybe — just maybe — his tremors will never spread to his left arm at all. “Any time you have tremors,” Clift says, as doctors tinker inside his head, "and the shaking goes away, that’s a miracle.”

Clift was a recipient of deep brain stimulation surgery, which for two decades has been used as a last-resort treatment for patients with Parkinson’s disease, an incurable, degenerative condition that affects millions of people worldwide. But a new decadelong surgery study at Vanderbilt offers a glimmer of hope for younger Parkinson’s patients. Although still far from a cure, the surgery study provides some of the first evidence that any medical treatment can slow the progression of tremors, the signature symptom of the disease.

Read more at the Tennessean