CMU Researchers Report New Cell-Targeted DBS

by James Cavuoto, editor

October 2021 issue

One of the challenges confronting neural engineers developing enhanced DBS systems is prolonging the effect of the stimulation. This would not only lead to longer battery life and reduce the need for subsequent surgeries, it would also likely improve the efficacy of DBS therapy.

A team of researchers at Carnegie Mellon University recently reported in Science on a new technique to make DBS more precise, resulting in therapeutic effects that outlast what is currently available. The work, led by Aryn Gittis and colleagues in CMU’s Gittis Lab, could significantly advance the study of Parkinson’s disease. “By finding a way to intervene that has long-lasting effects, our hope is to greatly reduce stimulation time, therefore minimizing side effects and prolonging battery life of implants,” said Gittis

Gittis set the foundation for this therapeutic approach in 2017, when her lab identified specific classes of neurons within the brain’s motor circuitry that could be targeted to provide long-lasting relief of motor symptoms in Parkinson’s models. In that work, the lab used optogenetics, a technique that cannot currently be used on humans. Since then, she has been trying to find a strategy that is more readily translated to patients suffering from PD. Her team found success in mice with a new DBS protocol that uses short bursts of electrical stimulation. “This is a big advance over other existing treatments,” Gittis said. “In other DBS protocols, as soon as you turn the stimulation off, the symptoms come back. This seems to provide longer lasting benefits—at least four times longer than conventional DBS.”

In the new protocol, the researchers target specific neuronal subpopulations in the globus pallidus, with short bursts of electrical stimulation. Gittis said that researchers have been trying for years to find ways to deliver stimulation in such a cell-type specific manner. “That concept is not new. We used a ‘bottom up’ approach to drive cell type specificity. We studied the biology of these cells and identified the inputs that drive them. We found a sweet spot that allowed us to utilize the underlying biology,” she said.

Neurosurgeons at Allegheny Health Network will use Gittis’ research in a safety and tolerability study in humans. Nestor Tomycz, a neurological surgeon at AHN, said that researchers will soon begin a randomized, double blind crossover study of patients with idiopathic PD. The patients will be followed for 12 months to assess improvements in their motor symptoms and frequency of adverse events.

“Aryn Gittis continues to do spectacular research that is elucidating our understanding of basal ganglia pathology in movement disorders. We are excited that her research on burst stimulation shows a potential to improve upon DBS which is already a well-established and effective therapy for PD,” Tomycz said.

Donald Whiting, CMO at AHN, said the new protocol could open doors for experimental treatments. “Aryn is helping us highlight in the animal model things that are going to change the future of what we do for our patients. She’s actually helping evolve the care treatment of Parkinson’s patients for decades to come with her research,” Whiting said.


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