In vagus research, the long-term odds just went up

Small packages: See the thing at the end of the wires? It's a pretty big deal.
By GREGORY ZELLER //

The latest bioelectronics breakthrough from the Feinstein Institutes for Medical Research is a long story. Literally.

But it’s a good one: For the first time, electric vagus nerve stimulation – usually tested through one-off zapping experiments – has been delivered through long-term implants.

And the results are more than promising, according to researchers who implanted the left cervical vagus nerve of four laboratory mice with “bipolar cuff electrodes” (know your microprobes, people) and left them there for months, stimulating the all-important vagus nerve bundle at scheduled intervals.

Based on two factors – inflammation plays a role in virtually every known disease, and inflammation responds to vagus nerve stimulation – bioelectronic medicine has been barging across the medical-science forefront. And VNS, a particular favorite of Feinstein Institutes President and CEO (and father of bioelectronic medicine) Kevin Tracey, has led the way.

Stavros Zanos: A way forward.

Fueled by a host of homegrown and recruited talent and numerous research grants, the Feinstein Institutes have emerged as a global leader in the field, with studies exploring potential VNS application for diabetes, postpartum hemorrhaging, hypertension and a walk-in clinic’s worth of other medical conditions.

Until now, those promising VNS tests have been limited to short-term stimulations – a timeframe of minutes to hours, due to the surgical and technological challenges of implanting electric stimulators small enough to fit laboratory mice (actually, the cervical vagus nerves of laboratory mice, which run about 1/3 of a millimeter).

Led by researcher Stavros Zanos, an assistant professor in the Manhasset research mecca’s Institute of Bioelectronic Medicine, scientists have now developed long-term implants that were still delivering expected VNS reactions – changes in breathing and heart rates, for instance – after 60 to 90 days, depending on the experiment.

What’s more, after the months-long tests, of the four mice implanted with those bipolar cuff electrodes, two enjoyed reduced inflammation associated with their mouse-modeled medical conditions – suggesting a “potential game-changing therapy for multiple chronic conditions,” according to the Feinstein Institutes.

Zanos, who collaborated with scientists at New York University and the University of Colorado in developing the next-gen implant tech, agreed that the results were promising for patients with acute-inflammation conditions.

“This indicates that even after several weeks, these implants can suppress inflammation,” Zanos told Innovate LI. “And it provides a way forward for testing long-term VNS in chronic inflammatory conditions like rheumatoid arthritis, pulmonary hypertension, Crohn’s disease and many others.”

Tracey called the long-term implants a “milestone” that would “accelerate advances in understanding basic mechanisms of bioelectronic medicine,” while Feinstein Institutes researcher Ibrahim Mughrabi, who presented the long-term VNS data at last week’s North American Neuromodulation Society 2020 Conference, noted researchers are “eager to continue to advance this new approach and look forward to the positive impact … on future bioelectronic research.”

Zanos, who heads up the Institute of Bioelectronic Medicine’s Translational Neurophysiology Lab, said he was confident the reassuring long-term study would open new doors in bioelectronics – and possibly redefine the field.

“We are hopeful that the success of the long-term stimulation implant will pave the way for a new standard in the way bioelectronic medicine research is conducted,” Zanos added. “By extending the time window of stimulation, researchers in labs across the globe will be able to get better, more in-depth data surrounding the expanding field of vagus nerve stimulation … and lead to further innovation.”