Salk Scientists Reveal Therapeutic Opportunities with Sonogenetics

In this process, scientists used ultrasonic waves—the same low-frequency waves used in medical sonograms—to activate a specific group of genetically marked cells.

The Salk Institute for Biological Studies announced that scientists have been able to activate human cells using ultrasound. It might sound like something out of science fiction, but the finding could have implications for new treatment options for neurological diseases, diabetes and heart problems.

The technique used in this study is called sonogenetics. In this process, scientists used ultrasonic waves—the same low-frequency waves used in medical sonograms—to activate a specific group of genetically marked cells.

This same group of scientists at Salk has studied this phenomenon for years. In 2015, Sreekanth Chalasani, associate professor at Salk’s Molecular Neurobiology Laboratory, and his associates researched sonogenetics on roundworms. The roundworm had a protein called TRP-4, which is a protein that is sensitive to low-frequency sounds. In an experiment, Chalasani’s team genetically added TRP-4 proteins to neurons that didn’t originally have them. The scientists found that the modified group of cells could be activated with a burst of ultrasound.

The same experiment was more difficult for human cells, though. Mammalian cells didn’t respond when researchers added the same TRP-4 protein. So Chalasani and his colleagues began to look for a different protein that might work instead. They began testing human cells in petri dishes at a frequency of 7 MHz, which is a safe range for humans to experience. After testing more than 300 different iterations of proteins, they finally found one: a channel protein called TRPA1. When the human cells were modified with TRPA1 and then exposed to ultrasound, the neurons lit up.

The scientists then began testing their hypothesis in mice. Using gene therapy, scientists added the gene for human TRPA1 to certain neurons into the brains of mice. The neurons were also modified to be white, which helped the scientists differentiate between the modified neurons and the original mouse neurons. When the scientists used the ultrasound machine, only the white neurons with the human TRPA1 genes activated.

The fascinating discovery holds significant potential for treating a variety of diseases.

“Gene delivery techniques already exist for getting a new gene—such as TRPA1—into the human heart. If we can then use an external ultrasound device to activate those cells, that could really revolutionize pacemakers,” Chalasani said.

Another use could be treating people with diabetes. Ultrasounds may be able to sense hemoglobin cells that indicate when someone’s blood sugar is too high or too low and could help administer insulin accordingly.

Sonogenetics could also help to treat neurological diseases. Currently, people with epilepsy, Parkinson’s disease and other neurological disorders may be treated with deep-brain electrical stimulation. In the 2015 study on roundworms, Chalasani and his colleagues discussed the advantages that ultrasound treatment would have. Neurological diseases are usually treated with electrical implantations, which require surgery to insert. But sonogenetics sound waves are non-invasive.

“This could be a big advantage when you want to stimulate a region deep in the brain without affecting other regions,” said Stuart Ibsen, a postdoctoral fellow at Salk who worked with Chalasani and was the first author on the roundworms study.

Full findings of the mammalian study will be published in Nature Communications on February 9.

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