New DBS Protocol Has Lasting Effects in Mice

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by Margarida Maia PhD |

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deep brain stimulation (DBS) protocol that targets specific sets of nerve cells, or neurons, in the brain produced long-lasting effects in a mouse model of Parkinson’s disease.

The new protocol, which uses brief bursts of electrical stimulation, offered effects that lasted hours longer than those of conventional DBS.

The study, “Population-specific neuromodulation prolongs therapeutic benefits of deep brain stimulation,” was published in the journal Science by a team of researchers at Carnegie Mellon University in Pittsburgh, Pennsylvania.

Surgery may be considered for patients with Parkinson’s who are not responding adequately to pharmacological treatment. The most common surgical treatment is DBS, which uses a battery-powered device called a neurostimulator (implanted just below the collarbone or in the abdomen) to send electrical signals to very fine wires implanted deep in the brain.

Motor symptoms of Parkinson’s occur when neurons in the areas of the brain that control movement — and the electrical signals they convey — are lost or fail to work properly. DBS is thought to interrupt these abnormal signaling pathways in the brain and rescuing motor function. However, DBS works only as long as stimulation is on, and it also has side effects.

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“DBS improves Parkinson’s disease symptoms acutely but does not differentiate between neuronal circuits, and its effects decay rapidly if stimulation is discontinued,” the researchers wrote.

“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,” the study’s lead author, Aryn Gittis, PhD, said in a press release.

The researchers hypothesized that targeting specific sets of neurons could make DBS more precise and long-lasting.

They used optogenetics — a technique that involves the use of light to control neurons that have been modified genetically to render them sensitive to light — to develop a  novel electrical stimulation protocol.

They focused on two sets of neurons in a brain region called the external globus pallidus: those expressing a protein called parvalbumin and those expressing a protein called lim-homeobox-6. Brief bursts of electrical stimulation were used to simultaneously stimulate the two sets — exciting the former and inhibiting the latter — in mouse models of Parkinson’s disease.

Excitatory and inhibitory signals are responsible for maintaining adequate stimulation of brain nerve cells. Excitatory signaling from one nerve cell to the next makes the latter cell more likely to fire an electrical signal, while inhibitory signaling makes the latter cell less likely to fire. This is the basis of communication between nerve cells in the brain.

“This is a big advance over other existing treatments,” said Gittis. “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.”

“We don’t yet understand every single piece of what’s going on in there, but our short burst approach seems to provide greater symptom relief,” the study’s first author, Teresa Spix, PhD, said. “A lot of times those of us that work in basic science research labs don’t necessarily have a lot of contact with actual patients. This research started with very basic circuitry questions but led to something that could help patients in the near future.”

A team of neurosurgeons at Pittsburgh’s Allegheny Health Network (AHN) will translate Gittis’ findings into a one-year clinical study in patients with idiopathic (or of unknown cause) Parkinson’s.

Its goal is to evaluate the safety, tolerability, and efficacy of the new protocol. The study is expected to begin soon.

“Aryn [Gittis] is helping us highlight in the animal model things that are going to change the future of what we do for our patients,” said Donald Whiting, MD, chief medical officer at AHN. “She’s actually helping evolve the care treatment of Parkinson’s patients for decades to come with her research.”

“This work is really going to help design the future technology that we’re using in the brain and will help us to get better outcomes for these patients,” added Nestor Tomycz, MD, neurological surgeon at AHN.

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