Researchers at Carnegie Mellon University have found a way to make deep brain stimulation (DBS) more precise, resulting in therapeutic effects that last longer than what is currently available. The work, led by Aryn Gittis and colleagues at CMU’s Gittis laboratory, will significantly advance the study of Parkinson’s disease.
DBS allows researchers and doctors to use thin electrodes implanted in the brain to send electrical signals to the part of the brain that controls movement. It is a proven way to help control unwanted movements in the body, but patients must receive continuous electrical stimulation to get relief from their symptoms. If the pacemaker is turned off, symptoms return immediately.
Gittis, an associate professor of biological sciences at Mellon College of Science and a professor at the Neuroscience Institute, said the new research could change that.
“By finding a way to intervene that has lasting effects, our hope is to dramatically shorten the stimulation time, thereby minimizing side effects and extending the battery life of the implants.”
Gittis laid the groundwork for this therapeutic approach in 2017, when his lab identified specific classes of neurons in the brain’s motor circuits that could be targeted to provide lasting relief from motor symptoms in models of Parkinson’s. In this work, the lab used optogenetics, a technique that uses light to control genetically modified neurons. Optogenetics, however, cannot currently be used in humans.
Since then, she has been trying to find a strategy more easily transposed to patients with Parkinson’s disease. His team succeeded in mice with a new DBS protocol that uses short periods of electrical stimulation.
“This is a big step up from other existing treatments,” Gittis said. “In other DBS protocols, as soon as you turn off the stimulation, the symptoms reappear. This appears to provide longer lasting benefits – at least four times longer than conventional DBS.”
In the new protocol, researchers target specific neuronal subpopulations in the globus pallidus, an area of the brain located in the basal ganglia, with short periods of electrical stimulation. Gittis said researchers have been trying for years to find ways to deliver stimulation in a cell-type specific way.
“This concept is not new. We used a ‘bottom-up’ approach to determine cell type specificity. We studied the biology of these cells and identified the inputs that drive them. We found a sweet spot that has us allowed to use the underlying biology, “she said.
Teresa Spix, the first author of the article, said that while there are many strong theories, scientists do not yet fully understand why DBS works.
“We’re kind of playing with the black box. We don’t yet understand every piece of what’s going on in there, but our short burst approach seems to provide greater symptom relief. The schema change allows us to affect cell types differently, ”she said.
Spix, who defended his doctorate. in July, is excited about the direct link between this research and clinical studies.
“A lot of times those of us who work in basic science research labs don’t necessarily have a lot of contact with real patients. This research started with very basic circuit questions, but has resulted in something that may help patients in the near future. Spix said.
Next, neurosurgeons at the Allegheny Health Network (AHN) in Pittsburgh will use Gittis’ research in a study of safety and tolerability in humans. Nestor Tomycz, neurological surgeon at AHN, said researchers will soon begin a double-blind, randomized crossover study in patients with idiopathic Parkinson’s disease. Patients will be followed for 12 months to assess improvements in their motor symptoms of Parkinson’s disease and the frequency of adverse events.
“Aryn Gittis continues to conduct spectacular research that elucidates our understanding of the pathology of the basal ganglia in movement disorders. We are delighted that his research on burst stimulation shows potential for improving DBS which is already a therapy. well established and effective for Parkinson’s disease, ”said Tomycz.
Donald Whiting, AHN’s chief medical officer and one of the country’s leading experts in the use of DBS, said the new protocol could open the door to experimental treatments.
“Aryn is helping us see things in the animal model that will change the future of what we do for our patients. She is actually helping to advance the treatment of Parkinson’s patient care for them. decades to come with his research, ”said Whiting.
Tomycz accepted. “This work is really going to help design the future technology that we use in the brain and will help us achieve better outcomes for these patients.”
The research was funded by the Richard King Mellon Foundation, the Lane Fellows Program, the Michael J. Fox Foundation, and the National Institutes of Health.