Research emerging from the US has devised a new method for refining the precision of deep brain stimulation, a treatment that may potentially transform the current landscape of treatment for Parkinson’s disease.
The work, conducted by researchers at Carnegie Mellon University and led by Associate Professor of Biological Sciences, Aryn Gittis, has discovered a novel method for prolonging the therapeutic effects of deep brain stimulation far beyond what is currently attainable.
The research looks to significantly enhance our knowledge of Parkinson’s disease, a devastating neurodegenerative disease that affects millions of people worldwide.
What is deep brain stimulation?
Deep brain stimulation enables medical professionals to utilise thin electrodes implanted in an individual’s brain to apply electrical signals to the regions of the brain that regulate movement. The technique is a tried and tested way of controlling unwanted movement in the body – a common symptom of Parkinson’s disease. However, this effect of overriding movement is only achievable through continuous deep brain stimulation, meaning that once the electrical stimulation stops, the symptoms immediately persist.
Gittis said: “By finding a way to intervene that has long-lasting effects, our hope is to greatly reduce stimulation time, therefore minimising side effects and prolonging the battery life of implants.”
Gittis’ team has been working toward this therapeutic approach since 2017, when her lab discovered specific classes of neurons located in the brain’s motor circuitry that could be targeted to achieve long-lasting relief from symptoms for people with Parkinson’s disease.
In that prior study, her team employed optogenetics, which involves utilising light to control genetically modified neurons, although this cannot currently be used on humans. Nevertheless, this endeavour inspired the researchers to design a method that can be implemented on patients with Parkinson’s disease, achieving success with a novel deep brain stimulation protocol that exerts short bursts of electrical stimulation.
“This is a big advance over other existing treatments,” Gittis said. “In other deep brain stimulation 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 deep brain stimulation.”
Constructing an innovative protocol
The team’s new technique targets specific neuronal subpopulations in the globus pallidus – located in the basal ganglia region of the brain – with short electrical stimulation bursts, a cell-type-specific approach that scientists have been trying to conduct for years.
Gittis commented: “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 utilise the underlying biology.”
The first author of the research, Teres Spix, said: “We’re sort of playing with the black box. 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 change in pattern lets us differentially affect the cell types.
“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.”
The next stage of the investigation will see neurosurgeons at Pittsburgh’s Allegheny Health Network (AHN) employ the protocol in a human safety and tolerability study, which will include a randomised, double-blind crossover study of patients with idiopathic Parkinson’s disease. The individuals will be followed for 12 months to analyse improvements in motor symptoms and adverse effects.
Nestor Tomycz, a neurological surgeon at AHN, said: “Aryn Gittis continues to do spectacular research which 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 deep brain stimulation, which is already a well-established and effective therapy for Parkinson’s disease. 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.”
Donald Whiting, the chief medical officer at AHN, commented: “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.”
