The National Institutes of Health (NIH) grant will fund the development of brain-on-a-chip technology, a microengineered device that incorporates nerve cells and blood vessels to help scientists better understand how neurodegenerative diseases such as Parkinson’s disease and Lewy body dementia affect function.
Jeongwook Baek, PhD, assistant professor of electrical and computer engineering at Binghamton University in New York, and co-investigator Myungeun Lee, PhD, assistant professor of chemistry at Drexel University in Philadelphia, were awarded a $414,191 grant to study how clumps of harmful alpha-synuclein protein spread in a disease-specific manner.
The research team will use an interdisciplinary approach combining biophysical methods, molecular biology and human organ-on-a-chip technology to more precisely determine how different cellular environments interact with alpha-synuclein aggregates at the molecular level.
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A chip containing neurons and blood vessels that mimic brain functions
“We are interested in how Lewy bodies spread to other brain regions and what factors influence their spread,” Peck said in a university news article. “Blood vessels, neurons, and possibly other cell types in the human brain may influence the progression of Parkinson’s disease.”
The formation of Lewy bodies (toxic aggregates of the protein α-synuclein found inside nerve cells) is thought to cause Parkinson’s disease by damaging and killing neurons that produce the chemical messenger dopamine. Loss of Lewy bodies interferes with normal brain function and causes a range of disease symptoms, from movement-related problems such as tremors, muscle stiffness and balance problems to non-movement-related problems such as cognitive and emotional impairment.
By using principles of electrical engineering to study how Lewy bodies form and spread in the brain, researchers hope to find new ways to address the progression of Parkinson’s disease and advance treatments for the disease.
The project involves developing brain-on-a-chip technology to investigate the relationship between alpha-synuclein accumulation and brain cells. Designed at a microscopic 3D level, the device mimics the structure and function of the human brain “with unprecedented physiological reality,” the researchers reported in a project summary submitted to the NIH.
“Animal models can help us understand complex pathophysiology (disease mechanisms) in the human body, but there are concerns about interspecies differences between animal and human physiology,” said Park, who is assisted by doctoral student Anika Alim in the university’s lab.
Aiming to advance the treatment of Parkinson’s disease and other synucleinopathies
By simulating protein-nerve cell interactions in a controlled laboratory environment, Paek hopes to uncover insights that could lead to more effective treatments for patients with neurodegenerative diseases and serve as a screening platform for therapies in development.
“The brain-chip established in this study may serve as a promising drug-screening platform that can faithfully reproduce cellular responses to pharmaceutical drugs,” the project summary states.
Paek’s research is based on a background in electrical engineering and previous experience in organic technologies, soft robotics (tissue-inspired systems), and synthetic modeling of human tissue. His curiosity in applying engineering principles to medical research led him to explore the connections between electrical and mechanical disturbances in the body and disease processes.
“Our bodies are highly dynamic, both mechanically and electrically, and disruptions to these biophysical signals can affect disease progression in different organs,” he said.
“Ultimately, this project will aid in the development of advanced diagnostic and therapeutic approaches for Parkinson’s disease and other synucleinopathies, thereby reducing the negative impact of neurodegenerative diseases on public health and societal functioning,” the lead researchers wrote.
Synucleinopathies are neurodegenerative disorders characterized by the aggregation of alpha-synuclein in neurons and glial cells, the cells of the nervous system that support neurons.
