A pacemaker-like device that ‘hacks’ the body’s neural circuits could alleviate symptoms of diseases from rheumatoid arthritis to Crohn’s, say researchers

A pioneering approach to tackling a host of diseases using an electrical implant could eventually reduce or even end pill-taking for some patients, researchers have claimed.

The technology relies on electrical stimulation of the vagus nerve – a bundle of nerve fibres that runs from the brain to the abdomen, branching off to organs including the heart, spleen, lungs and gut, and which relays signals from the body’s organs to the brain and vice versa.

The pacemaker-like device is typically implanted below the left collarbone with wires running to the vagus nerve in the neck and is already used to tackle treatment-resistant epilepsy and depression.

But a growing body of researchers say that such “hacking” of the body’s neural circuits could alleviate the symptoms of diseases including rheumatoid arthritis and Crohn’s disease by tapping into a recently discovered link between the brain and the immune system.

That, they say, could bring hope for those with currently untreatable conditions while raising the possibility for others of dramatically reducing medication, or even cutting it out altogether.

“In your lifetime and mine we are going to see millions of people with devices so they don’t have to take drugs,” said Kevin Tracey, president of the Feinstein Institute for Medical Research and co-founder of bioelectronics company, SetPoint Medical.

Among the studies fuelling the excitement is research published by Tracey and colleagues last year: of the 17 patients with rheumatoid arthritis involved in a clinical trial, more than two-thirds had at least a 20% improvement in their disease, with two entering remission.



“Within six weeks I felt no pain. The swelling has gone. I go biking, walk the dog and drive my car. It is like magic,” Monique Robroek, a participant in the team’s research told Sky News in 2014.

Dubbed “bioelectronics”, the field is no fringe affair, with research groups around the world as well as companies including General Electric, GlaxoSmithKline and Google entering the fray; the US National Institutes of Health has also awarded $20m towards research in the field.



The premise is novel. While conventional medicine looks to tackle the presence of certain problematic molecules using drugs, bioelectronics instead looks to manipulate the neural circuits behind the release of such molecules. “Every cell in the body is within shouting distance of a neuron,” said Tracey.

The approach builds on the so-called “inflammatory reflex” – a process discovered by Tracey by which information on tissue damage and inflammation is sent to the brain via the vagus nerve, which then sends signals back down to organs to dampen the inflammation.

“It is really exciting because for decades we thought the brain had no influence on our immune system whatsoever,” said Matthijs Kox , an expert in immune responses from Radboud university medical centre in the Netherlands.

The key to tackling diseases like rheumatoid arthritis is tumor necrosis factor (TNF) – a substance involved in inflammation that is primarily released from white blood cells called macrophages, found in the spleen and elsewhere in the body.

Drugs currently used to bind to TNF and block its activity are big business, but they do not work for everyone and side effects can include an increased risk of cancer.

The bioelectronic approach, on the other hand, uses stimulation of the vagus nerve to switch off the release of TNF. The route is believed to be indirect, with the activated vagus nerve communicating to nerves in the spleen, increasing their release of neurotransmitters. This has a knock-on effect on immune cells known as T-cells, increasing their release of substances which in turn reduce the release of TNF from macrophages.

However, Kox notes that this pathway is probably more complex, with research suggesting the neurotransmitters from the vagus nerve itself could also more directly affect the macrophages.

And while Tracey and others have shown such a link between vagus nerve activation and TNF levels in rodents, research in humans remains limited. “There are a lot of ifs and unknowns,” said Kox, adding that the study by Tracey and colleagues involved relatively few people.



But does this mean that these autoimmune diseases could, at least in part, be down to a problem with the activity of the vagus nerve? Maybe, says Tracey.

The vagus nerve is key controlling to heart rate, and research has found that patients with rheumatoid arthritis and those at risk of the disease have a higher heart rate than healthy individuals. “Some would argue that the vagus nerve impairments have been known for decades,” said Tracey. “[But] everyone thought it was caused by the disease.”



While Kox is excited by the field of bioelectronics, he said his own research into the latter part of the proposed pathway has shown mixed results.

Meanwhile, researchers behind a pilot study in the UK involving 15 people with the immune system disorder Sjögren’s syndrome say the approach is showing promising results.

Nevertheless the technology is in development. Tracey and colleagues have created a programmable jelly bean-sized device that sits on the vagus nerve and can be charged using a collar and controlled by a tablet computer. But Tracey is adamant that the key to developing bioelectronics lies in understanding the body’s mechanisms.

“Everybody keeps talking about [how] we need smaller electrodes to hit individual nerve fibres – I think that is baloney juice,” he said.

While the vagus nerve is packed with more than 100,000 nerve fibres “like a transatlantic cable”, Tracey notes that fewer than 2,000 are linked to the spleen with these fibres “low threshold” – a feature that means they can be specifically targeted.

“We can put a cuff on the whole nerve, but if you put in a small amount of current, the only fibres that get stimulated are the low threshold [ones],” said Tracey, adding that the frequency of the current, and its amplitude, can also be modified. This could offer further ways to hone activation and target specific responses.

That said, figuring out exactly what combination triggers which responses is no mean feat and decoding the signals is an ongoing project.

But bioelectronics offers other attractions. Using vagus nerve activation, levels of TNF are reduced, rather than completely blocked – a feature Tracey notes could potentially avoid problems of immunosuppression seen for TNF-blocking drugs. What’s more, the bioelectronic approach also reduces levels of other molecules in the spleen linked to inflammation, suggesting the technique might offer hope to those for whom TNF-blocking drugs have failed.

Kox was cautiously optimistic about the future for bioelectronics. “I am a bit reluctant to say that it is the magic bullet or something, but it is certainly a very interesting pathway and could be very relevant to those kinds of diseases [like rheumatoid arthritis],” he said. “The goal is of course to alleviate symptoms and maybe to taper down medication – but that is still a long way down the road.”

But Tracey believes the new treatments could help to tackle conditions as diverse as diabetes, high blood pressure, cancer and sepsis: “This is the tip of the iceberg.”

It sounds disconcertingly like that most eyebrow-raising of remedies: a panacea. But if Tracey’s optimism pays off, the next generation of hackers could be wearing white coats.