Imagine a day when you go to the doctor and, instead of a prescription on paper, you come out with a tiny device attached to your nervous system and possibly a new app on your phone. No more worrying about what time you have to take a pill – all you need to do is let technology do its business. Believe it or not, this day may not be that far away.

The human nervous system is the bioelectrical infrastructure of your body. Now imagine you could hack it. Welcome to the field of bioelectronic medicine. It’s an area that asks: what if, instead of using drugs to treat a condition, implants could control and tweak our body’s functions? What if, somewhere down the line, you could combat a tumour by harnessing your neural signals?

The idea may sound far-flung, but the research around it has roots in one of the most common bodily responses – one that most of us have likely experienced at one point or another.

Understanding inflammation

For Dr Kevin Tracey, based at the Feinstein Institute for Medical Research in New York, and one of the pioneers in this field, it all started with a desire to understand inflammation. For years, his team studied how and why the body reacts so dramatically to inflammatory conditions, such as rheumatoid arthritis and psoriasis, and why these diseases are so difficult to treat.

In patients with rheumatoid arthritis, for example, current treatments typically involve prescription drugs to block the production of a protein called tumour necrosis factor (or TNF for short), which the body generates in excess in case of inflammation. However, there are many problems with blocking TNF – not least the high price of treatment and potentially life-threatening side effects.

“Despite the importance of the TNF drugs, up to half of the patients are not optimally treated and are not cured,” says Tracey. “They continue to have pain and they need other options. We also know that these drugs are extremely expensive, and some patients are afraid of taking those drugs because they have significant side effects.” These include increased risk of cancer and cardiovascular diseases, to name just a few.

Tracey’s hope was to find potential new targets to develop more effective drugs, but instead they stumbled on a surprising connection: they realised that, in the case of inflammation, TNF production is controlled by the immune system, which in turn is controlled by the nervous system.

Finally, after 15 years of research, the team had their target. It wasn’t what they had anticipated, but the vagus nerve (which runs down our neck), turned out to be the link between the brain and the TNF response. “We mapped the neurological circuits that originate in the brain and control TNF production in the body,” explains Tracey. “We discovered that those circuits travel in the vagus nerve, one of the body’s major nerves that connects the immune system to the brain.”

At this stage – comparing the brain to a computer – the idea was to “hack” the nervous system as an indirect way to control TNF production. Following this approach, they found out that it’s possible to control the activity of the vagus nerve by stimulating it with a low-voltage current, using a small implantable device inserted in the neck.

“You can change the frequency, you can change the amplitude”

“You can change the frequency, you can change the amplitude, you can change the voltage, and by changing those parameters, we’re able to stimulate the fibres that control TNF without a significant effect on heart rate. Patients can have their TNF blocked without experiencing stimulation of the other fibres that control other sites,” says Tracey.

Published only a few months ago, this study was a milestone, as one of the first clinical trials in humans to use small implantable devices instead of drugs to treat a condition. The results were positive and patients with rheumatoid arthritis saw their symptoms improve significantly during the treatment.

This astonishing finding was a breakthrough. For rheumatoid arthritis patients, the idea of bioelectronic medicine is no longer to control TNF production directly (with prescription anti-TNF drugs), but to target the neural circuits that control the part of the immune system that controls TNF production (with implantable devices). “Once you think in terms of neurons controlling immune cells, you can develop devices that use electrons to control the nerves, to control the immune cells, to control the TNF,” says Tracey.

Wide range of applications

This sounds incredible, but you might argue that if it can only be used to treat inflammation, it has limited use. Even if it could only be applied to inflammation, it’s coming to light just how important this bodily response is for many seemingly unrelated conditions, from diabetes and hypertension to arteriosclerosis and even cancer. However, the true potential for this approach comes from the fact that virtually every mechanism in our body is regulated through our nervous system.

Think about it as a control tower at the airport: each pilot may be in charge of its own plane, but ultimately, they all have to take orders from the control tower. At the risk of sounding like a terrorist attack, if you “hack” into the control tower, you’ll have control of all the planes. (In other words, if you control the nervous system, you have control of virtually all bodily functions.)

For the scientific community, the massive challenge ahead is to identify the neural circuits that control other targets in the body, which may be used to treat more conditions. “The race now is to find mechanisms that can be targeted with future devices,” says Tracey. The day will come when it will be common practice to control insulin levels in diabetics, regulate food intake in obese patients, or adjust high blood pressure in those with cardiovascular conditions with one of these devices.

Future devices

Sadly, we’re not there yet, and if there’s work to do on the physiology side, there’s also plenty of work to do on the technology side. At the moment, the implants are too big, the batteries don’t last long and with all the wires and cables, they eventually cause scar tissue to form. In addition, conventional technologies are not able to record information with high accuracy or record from multiple sites in a nerve bundle.

Based at the University of California, assistant professor Michel Maharbiz leads one of the teams trying to solve some of these issues. “One of the problems that we’re interested in,” says Maharbiz, is that “neural implants cannot survive for years and years in the body”. According to the researcher, this “has to do with the materials, it has to do with the size of the implant, it has to do with whether there are wires and tethers”.

(Above: “Neural dust” sensor on a fingertip, from UC Berkeley)

Smaller implants are certainly one way to go, but there are also other avenues to explore. “I think that this technology will go beyond just recording from the nervous system, to recording other information from organs to do preventive health, or to track the state of a tumour,” says Maharbiz. “You don’t have to measure just nerve activity – you can measure oxygen, pH, temperature. There are many things that one can measure with a general application.”

“This technology is really maturing”

“From a technology perspective, I think it’s a wonderful time,” he adds. “This technology is really maturing, and there’s real hope that in the next decade you’re going to start seeing systems in humans that last a very long time, [which] have many channels and really allow multiple readings.”

It’s not going to be next week but, when all this becomes possible, it’s not hard to imagine routine use of these implants for many different conditions. Given the scope of what bioelectronic treatment stands to achieve, this really could be the future of medicine.



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