Unlocking the Promise of Bioelectronics

The Feinstein Institute for Medical Research

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In Bosnia, a truck driver was crippled by rheumatoid arthritis. His joints inflamed, he was unable to work, drive, or play with his children. After years of disability and pain, he volunteered for a clinical trial of a vagus nerve stimulator being conducted by a start-up company, SetPoint Medical, Inc. Eight weeks later, his arthritis was in remission, and the man was able to return to work and to resume a normal life as a father for the first time in years.

Kevin J. Tracey, president of the Feinstein Institute for Medical Research and inventor of the vagus nerve stimulator to treat inflammation, traveled to Bosnia to meet the patient and see his remission in person. Tracey returned to the United States hoping that he had witnessed the first clinical results for an entirely new modality to treat inflammation. Devices like the vagus nerve stimulator, termed "bioelectronics," may offer promise to those who, like the truck driver, have become prisoners to their own immune responses.

"To me, nothing is more fulfilling than meeting a patient who has benefited from a discovery made in the lab," says Tracey. "This experience—of inventing a treatment and transforming someone's life for the good—is a stark reminder that successful inventions require more than just the idea; they require solidarity, tenacity, dedication, and time."

Founded in 1999, the Feinstein Institute for Medical Research is a nonprofit organization that provides a research base for the kind of life-altering scientific innovation Tracey pursues. As part of North Shore-LIJ Health System, the largest integrated healthcare network in New York, the Feinstein Institute is responsible for as many as 2,000 clinical studies at any given time, involving 15,000 patients each year. The president of the Feinstein Institute since 2005, Tracey has helped build the Institute into a leading center for the study of immunology and neuroscience.

"This experience—of inventing a treatment and transforming someone's life for the good—is a stark reminder that successful inventions require more than just the idea; they require solidarity, tenacity, dedication, and time."

After 20 years of targeted research, Tracey understands how the body's natural response to disease can cause pain, further illness, and—in the case of sepsis, which Tracey has called "the killer within,"—even death.

Tracey first discovered the role of the vagus nerve in suppressing inflammation while researching an experimental molecule called CNI-1493, which he hypothesized could be used to stop the swelling in the brain that occurs after a stroke. Tracey and his team found that CNI-1493 stimulated signals in the vagus nerve which traveled from the brain to the major organs and stopped inflammation in the body's organs.

"The drug was stimulating the vagus nerve and turning the brake on the immune system," Tracey told Wired earlier this year. "Once we understood that, it was a 'eureka' moment. We realized you didn't need the drugs, you could just manipulate the nerve itself."

It sounds like science fiction, but the idea has an undeniable elegance. Instead of introducing chemicals, why not electrically stimulate the nerves to produce the anti-inflammatory effect?

Tracey dove into the research of bioelectronics hoping to prove that if the neural signature of a disease can be mapped, the disease can be treated by electrical impulse alone. The treatment for the Bosnian man's arthritis by SetPoint Medical was the first human trial of this theory, and Tracey is hoping for more, similar, successes.

While such treatment may not be able to rid the body of infectious diseases or cancer, it can help patients cope with their symptoms, and stimulate the immune system to better fight illness. Bioelectronics could have a direct impact on a range of inflammatory diseases—not just arthritis, but asthma, diabetes, and even neuro-psychiatric disorders like Parkinson's and epilepsy. The field offers stunning opportunities for research across a wide variety of disciplines, and a recent comment in Nature called for trans-disciplinary cooperation:

"To develop treatment devices in this field, bioengineers designing biocompatible interfaces will need to collaborate with electrical engineers to develop microchips for real-time signal processing; with nanotechnologists to create energy sources; and with neurosurgeons to ensure that these designs can be implanted and connected. Researchers will need to embrace the languages and tools of other fields, and perhaps even dream differently: much of the challenge lies in translating biological understanding into engineering specifications."

Tracey's research is being funded by the NIH, DARPA, and GlaxoSmithKline (GSK), which see bioelectronics as an incredible opportunity. The pharmaceutical giant GSK has committed to funding up to 40 researchers in up to 20 labs as the race to map disease-associated neural circuits heats up.

Of course bioelectronics are only one area of focus for Feinstein Institute researchers; they are conducting high-profile research projects in areas such as Parkinson's disease, genomics, and schizophrenia management, hoping to impact patient's lives throughout a range of diseases and conditions, as nearby as New York, and as far away as Bosnia.

Photo: Kevin J. Tracey (center) with a few of his lab members.