AhSonogenetics: A New Era in Noninvasive Brain Treatment

In a significant breakthrough, the research team at Washington University in St. Louis has introduced AhSonogenetics, a noninvasive technology that ingeniously combines a holographic acoustic device with cutting-edge genetic engineering. Led by Hong Chen, an associate professor of biomedical engineering at the McKelvey School of Engineering and of neurosurgery at the School of Medicine, this groundbreaking method offers unprecedented accuracy in targeting and modulating neurons affected by neurodegenerative diseases such as Parkinson’s.

AhSonogenetics leverages the capabilities of a wearable ultrasound device to selectively influence genetically modified neurons in the brains of mice. Detailed in a study published on June 17, 2024, in the Proceedings of the National Academy of Sciences, this pioneering approach sets the stage for transformative interventions in neurodegenerative conditions that often impact multiple brain regions. “By enabling precise and flexible cell-type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders,” remarked Chen.

The journey towards AhSonogenetics is deeply rooted in Chen’s earlier innovative work. In 2021, her team introduced Sonogenetics, a method that utilized focused ultrasound to deliver viral constructs containing ultrasound-sensitive ion channels to genetically selected neurons. This technique employed low-intensity focused ultrasound to generate a small burst of warmth, thus opening the ion channels and activating the neurons. Notably, Chen’s team was the first to demonstrate that sonogenetics could modulate the behavior of freely moving mice.

Building on this foundation, Chen’s lab made further advancements in 2022 by designing and 3D-printing an Airy beam-enabled binary acoustic metasurface. This development allowed for the precise manipulation of ultrasound beams, culminating in Sonogenetics 2.0. This enhanced technique combined the strengths of ultrasound and genetic engineering, enabling noninvasive and precise modulation of neurons in both humans and animals. AhSonogenetics represents the culmination of these advancements, offering a method capable of addressing multiple affected brain regions simultaneously with unparalleled precision and flexibility. “Airy beam is the technology that can give us precise targeting of a smaller region than conventional technology, the flexibility to steer to the targeted brain regions, and to target multiple brain regions simultaneously,” explained Yaoheng (Mack) Yang, a postdoctoral research associate.

The efficacy of AhSonogenetics was tested in a mouse model of Parkinson’s disease, characterized by motor deficits such as slow movements, difficulty walking, and freezing behaviors. Utilizing this new technology, Chen’s team successfully stimulated two brain regions simultaneously in a single mouse, eliminating the need for multiple implants or interventions. This dual-region stimulation alleviated Parkinson’s-related motor deficits in the model. The Airy-beam device not only surpasses the limitations of traditional sonogenetics but also proves to be cost-effective, with each device costing approximately $50 to fabricate.

“This technology can be used as a research platform to speed neuroscience research because of the capability to flexibly target different brain regions,” noted Zhongtao Hu, a former postdoctoral research associate and one of the first authors of the study. “The affordability and ease of fabrication lower the barriers to the widespread adoption of our proposed devices by the research community for neuromodulation applications.”

The implications of AhSonogenetics reach far beyond Parkinson’s disease. This versatile technology holds potential for adaptation to other neurological disorders such as Alzheimer’s disease, epilepsy, and chronic pain. Its ability to noninvasively and precisely modulate specific neuron types could significantly reduce reliance on pharmaceutical interventions, offering a promising non-drug-based approach. The affordability and ease of fabrication make AhSonogenetics accessible for widespread research use, democratizing the technology and accelerating the pace of neuroscience discoveries. By enabling real-time adjustments during neuromodulatory treatments, the technology could further enhance therapeutic efficacy. Researchers could monitor patients’ responses and fine-tune the stimulation parameters accordingly, paving the way for highly personalized neuromodulation therapies.

AhSonogenetics is poised to revolutionize the field of neuromodulation by offering a noninvasive, precise, and flexible tool for investigating and treating a broad spectrum of neurological disorders. The open-source design file available on GitHub fosters collaborative advancements, inviting researchers worldwide to contribute to and benefit from this groundbreaking technology. This collective effort could lead to new insights into brain functions and disorders, ultimately transforming the landscape of neurodegenerative disease research and treatment.

The future of AhSonogenetics looks promising with several potential developments on the horizon. Broader applications could see the technology adapted for conditions like Alzheimer’s disease, epilepsy, and chronic pain. Its versatility in targeting multiple brain regions makes it a valuable tool for various applications. Integration with other neuromodulation technologies, such as optogenetics or transcranial magnetic stimulation, could enhance its efficacy, offering more comprehensive treatment options. The technology’s precision and flexibility could lead to personalized neuromodulation therapies tailored to individual patients’ needs, improving treatment outcomes and reducing side effects. Additionally, the ability to make real-time adjustments during neuromodulatory treatments could optimize therapeutic effects, allowing researchers to monitor patients’ responses and fine-tune the stimulation parameters accordingly. The open-source design file on GitHub fosters collaboration among researchers, enabling the scientific community to collectively advance the technology and explore new applications.

AhSonogenetics represents a significant paradigm shift in the field of neuromodulation, offering a noninvasive, precise, and flexible tool for investigating and treating neurological disorders. As the technology continues to evolve, it holds the promise of transforming the landscape of neurodegenerative disease research and treatment, bringing hope to millions affected by these debilitating conditions. The journey from Sonogenetics to AhSonogenetics is a testament to the relentless pursuit of innovation and the potential of interdisciplinary collaboration in advancing human health.

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