‘First-in-class’ tool for potential treatment of brain disorders

Hong Chen, medical school faculty to collaborate on NIH-funded work

Beth Miller  
Hong Chen

New methods to treat human brain disorders is one of the top priorities of the National Institutes of Health’s ambitious BRAIN Initiative. To find noninvasive tools that are equally or more effective is a kind of Holy Grail for neuroscience, and a biomedical engineer at Washington University in St. Louis has it in her sights. 

Hong Chen, associate professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology in the School of Medicine, plans to develop and validate an incisionless treatment delivery method —named iSonogenetics — in animals with a three-year, $2.1 million grant from the National Institutes of Health’s National Institute of Mental Health. The uniquely structured UG3/UH3 grant provides initial support for three years to develop the tool in the UG3 phase with two additional years of funding in the UH3 phase to validate its performance.

Chen will collaborate with Ilya Monosov, associate professor of neuroscience and co-principal investigator, and three other faculty members from the School of Medicine: Joel Perlmutter, MD, professor of neurology; Buck Rogers, professor of radiation oncology; and Larry Snyder, MD, PhD, professor of neuroscience.

Chen’s iSonogenetics method uses focused ultrasound to deliver a viral construct containing ultrasound-sensitive ion channels to genetically selected neurons in the brain through the nose. Then, they use low-intensity focused ultrasound to deliver a small burst of warmth, which opens the ion channels and activates the neurons.  

“This research is significant because it directly addresses the central goal of this aspect of the BRAIN Initiative by providing the neuroscience community with a first-of-its-kind tool that has the potential to change the way we approach these process and to uncover new ways to understand and treat these neurological disorders,” Chen said.

The work’s foundation is in optogenetics, the combination of the targeted expression of light-sensitive ion channels and the precise delivery of light to stimulate neurons deep in the brain. While optogenetics has increased the discovery of new neural circuits, it is limited in penetration depth due to light scattering and requires surgical implantation of optical fibers. The iSonogenetics method requires no surgery.

Earlier this year, Chen’s team demonstrated the feasibility of this method in a mouse model in research published in Brain Stimulation, which to date is the most downloaded article in the journal. That work provided evidence that this method prompts behavioral responses in the mice by targeting a deep brain site.

“iSonogenetics can potentially achieve noninvasive and cell-type-specific neuromodulation at deep brain targets with a high spatiotemporal resolution,” Chen said. “Our ultimate goal is to use iSonogenetics to modulate human brains to identify the neuronal bases of behavior and to progress toward the targeted treatment of human brain disorders, such as Parkinson’s disease.”

The McKelvey School of Engineering at Washington University in St. Louis promotes independent inquiry and education with an emphasis on scientific excellence, innovation and collaboration without boundaries. McKelvey Engineering has top-ranked research and graduate programs across departments, particularly in biomedical engineering, environmental engineering and computing, and has one of the most selective undergraduate programs in the country. With 165 full-time faculty, 1,420 undergraduate students, 1,614 graduate students and 21,000 living alumni, we are working to solve some of society’s greatest challenges; to prepare students to become leaders and innovate throughout their careers; and to be a catalyst of economic development for the St. Louis region and beyond.

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