Can DBS for Parkinson’s Disease Become More Targeted?

Using an animal model, the researchers said they recently found a way to refine deep brain stimulation (DBS) and make it more precise for 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 achieve relief from their symptoms. If the pacemaker is turned off, symptoms return immediately.

Previous work has identified specific classes of neurons in the brain’s motor circuits that could be targeted to provide lasting relief from motor symptoms in Parkinson’s models. In this work, the scientists used optogenetics, a technique that uses light to control genetically modified neurons. Optogenetics, however, cannot currently be used in humans.

In the latest research, published in Science, the researchers used a new DBS protocol that uses short periods of electrical stimulation in mice. In the protocol, researchers target specific neuronal subpopulations in the globus pallidus, an area of ​​the brain in the basal ganglia, with these short electrical impulses.

“This is a big step up from other existing treatments,” Aryn Gittis, PhD, associate professor of biological sciences at Carnegie Mellon Universty College of Science and professor at the Neuroscience Institute, said in a statement. “In other DBS protocols, as soon as you turn off the stimulation, the symptoms return. This appears to provide longer lasting benefits, at least four times longer than conventional DBS. “

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 have studied the biology of these cells and identified the inputs that drive them. We found a sweet spot that allowed us to use the underlying biology, ”she said. “By finding a way to intervene that has lasting effects, our hope is to dramatically reduce the stimulation time, thereby minimizing side effects and extending the battery life of the implants.”

Scientists do not yet fully understand why DBS works, said Teresa Spix, PhD, the first author of the article, although there are many solid theories. In the next phase of research, 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 and the frequency of adverse events.

Reference

Spix TA, Nanivadekar S, Toong N, et al. Population-specific neuromodulation extends the therapeutic benefits of deep brain stimulation. Science. 2021; 374; 201-206. doi: 10.1126 / science.abi7852