Could Sound Replace Pacemakers and Insulin Pumps?

Imagine a future in which crippling epileptic seizures, faltering hearts and diabetes could all be treated not with scalpels, stitches and syringes, but with sound. Though it may seem the stuff of science fiction, a new study shows that this has solid real-world potential.

Sonogenetics – the use of ultrasound to non-invasively manipulate neurons and other cells – is a nascent field of study that remains obscure amongst non-specialists, but if it proves successful it could herald a new era in medicine.

In the new study published in Nature Communications, researchers from the Salk Institute for Biological Studies in California, US, describe a significant leap forward for the field, documenting their success in engineering mammalian cells to be activated using ultrasound. The team say their method, which they used to activate human cells in a dish and brain cells inside living mice, paves the way toward non-invasive versions of deep brain stimulation, pacemakers and insulin pumps.

Going wireless is the future for just about everything,” says senior author Dr Sreekanth Chalasani, an associate professor in Salk’s Molecular Neurobiology Laboratory. “We already know that ultrasound is safe, and that it can go through bone, muscle and other tissues, making it the ultimate tool for manipulating cells deep in the body.

Chalasani is the mastermind who first established the field of sonogenetics a decade ago. He discovered that ultrasound sound waves beyond the range of human hearing — can be harnessed to control cells. Since sound is a form of mechanical energy, he surmised that if brain cells could be made mechanically sensitive, then they could be modified with ultrasound.

In 2015 his research group provided the first successful demonstration of the theory, adding a protein to cells of a roundworm, Caenorhabditis elegans, that made them sensitive to low-frequency ultrasound and thus enabled them to be activated at the behest of researchers.

Chalasani and his colleagues set out to search for a new protein that would work in mammals. Although a few proteins were already known to be ultrasound sensitive, no existing candidates were sensitive at the clinically safe frequency of 7MHz – so this was where the team set their sights. To test whether TRPA1 protein could activate cell types of clinical interest in response to ultrasound, the team used a gene therapy approach to add the genes for human TRPA1 to a specific group of neurons in the brains of living mice. When they then administered ultrasound to the mice, only the neurons with the TRPA1 genes were activated.

Clinicians treating conditions including Parkinson’s disease and epilepsy currently use deep brain stimulation, which involves surgically implanting electrodes in the brain, to activate certain subsets of neurons. Chalasani says that sonogenetics could one day replace this approach—the next step would be developing a gene therapy delivery method that can cross the blood-brain barrier, something that is already being studied. Perhaps sooner, he says, sonogenetics could be used to activate cells in the heart, as a kind of pacemaker that requires no implantation.