As the race to find a cure for Parkinson’s disease continues, UC Berkeley neurobiologist Yang Dan will join a $9 million project to study brain circuitry issues around the disease.
The project — which was recently awarded the funding over the next three years by the Aligning Science Across Parkinson’s initiative — aims to better understand Parkinson’s causes, its progression and the underlying brain circuitry driving its symptoms.
It is led by Dalton James Surmeier, a professor and chair of neuroscience at Northwestern University’s Feinberg School of Medicine. Surmeier said the project also involves a team of international researchers with different specialties, including Dan, who will bring her background in sleep science.
“If we’re going to develop a cure, we have to understand the causes of the disease more clearly,” said Surmeier. “By better understanding the causes of those symptoms, the dysfunction in the brain that drives them … we’ll be able to develop therapies that more effectively treat those symptoms.”
Parkinson’s is a neurodegenerative disease that produces symptoms like movement issues and tremors, according to the Parkinson’s Foundation. While causal effects were initially unclear, Surmeier’s team confirmed that mitochondrial “powerhouse” failures in brain cells that make dopamine — a neurotransmitter essential for movement — causes some forms of the disease.
By mimicking these dysfunctions in mice brains, Surmeier said his team was able to create mice with Parkinson’s symptoms. This discovery may help researchers detect the disease earlier and treat it better, Surmeier added.
“That’s an indication that we were onto something — that in fact, the mouse was displaying a human-like staging of its disease,” Surmeier said.
While it was commonly thought that Parkinson’s symptoms develop when dopamine becomes depleted at a part of the brain called the basal ganglia, Surmeier said his team discovered animals only experience symptoms when dopamine was lost at the substantia nigra, a specific part of the basal ganglia.
This discovery was significant in treating Parkinson’s symptoms since the small size of the substantia nigra allowed for a single injection to effectively cover the area with gene therapy.
“It suggests that humans who are suffering from late-stage Parkinson’s disease may very well be very effectively treated by this gene therapy not targeting the strida but targeting the substantia nigra,” Surmeier said.
Dan noted that she will examine a part of the basal ganglia called the SNr, or substantia nigra pars reticulata, and its role in affecting sleep and motor activity in Parkinson’s patients.
She and her team will use techniques such as optogenetics and electrophysiology to study the impacts of SNr on sleep in Surmeier’s mouse model.
“Our hope is to facilitate the development of better PD treatment,” Dan said in an email. “There is evidence that poor sleep is not only the consequence of PD but could also contribute to PD progression, so improving sleep in early stages of PD could even slow down disease progression.”