How tiny bioelectronic implants could one day replace pharmaceutical drugs

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Could a small electronic device treat certain diseases safer and more effectively than pharmaceutical drugs?

For Kelly Owens, the answer was clear. She spent over a decade suffering from Crohn’s disease, a chronic inflammatory bowel disease that left her with severe arthritis in her joints. The pain forced her to use a cane, sometimes a wheelchair. She tried over 20 medications and racked up over $ 1 million in medical bills, but her condition did not improve.

A doctor told Owens and her husband that they shouldn’t have children and that she should take steroids for life.

Then Owens turned to bioelectronic medicine. She contacted Dr Kevin Tracey, a pioneer in the field and CEO of the Feinstein Institutes for Medical Research in New York. Soon after, Owens and her husband moved to Amsterdam to participate in a clinical trial involving a relatively new bioelectronic approach to treating inflammation.

Doctors implanted a small electronic device in her chest that stimulated her vagus nerve, the body’s longest cranial nerve. After two weeks, Owens no longer needed a cane or wheelchair. Soon she was jogging on a treadmill.

A growing body of research in bioelectronic medicine shows that it is possible to treat diseases by manipulating the nervous system. The field is essentially a fusion of neurosciences, molecular biology and neurotechnology. Dr Tracey and her colleagues believe that the field could one day replace or supplement many pharmaceutical drugs used to treat major diseases, including cancer and Alzheimer’s disease.

But how? The answer centers on how the nervous system controls molecular processes in the body.

… The most revolutionary aspect of bioelectronic medicine, according to Dr. Tracey, is that approaches like vagus nerve stimulation would not lead to harmful and potentially fatal side effects, as many pharmaceutical drugs currently do.

You accidentally put your hand on a hot stove. Almost instantly, your hand pulls back.

What triggered the movement of your hand? The answer is not that you have consciously decided that the stove is hot and that you need to move your hand. Rather, it was a reflex: the skin receptors in your hand sent nerve impulses to the spinal cord, which ultimately sent back the motor neurons that caused your hand to move. All of this happened before your “conscious brain” realized what happened.

Likewise, the nervous system has reflexes that protect individual cells in the body.

“The nervous system has evolved because we have to react to environmental stimuli,” said Dr. Tracey. “Neural signals don’t come from the brain first. Instead, when something is happening in the environment, our peripheral nervous system senses it and sends a signal to the central nervous system, which includes the brain and spinal cord. And then the nervous system reacts to correct the problem.

So what if scientists could “hack” the nervous system, manipulating the electrical activity of the nervous system to control molecular processes and produce desirable results? This is the main goal of bioelectronic medicine.

“There are billions of neurons in the body that interact with almost every cell in the body, and at each of these nerve endings, molecular signals control molecular mechanisms that can be defined and mapped, and potentially controlled,” said Dr. Tracey. in a TED Conference.

“Many of these mechanisms are also involved in important diseases, such as cancer, Alzheimer’s disease, diabetes, hypertension and shock. It is very plausible that the discovery of neural signals to control these mechanisms holds promise for devices replacing some of the current drugs for these diseases. “

How can scientists hack the nervous system? For years, researchers in bioelectronic medicine have focused on the longest cranial nerve in the body: the vagus nerve.

What’s more, clinical trials show that vagus nerve stimulation not only ‘stops’ inflammation, but also triggers the production of cells that promote healing.

Electrical signals, seen here in a synapse, travel along the vagus nerve to trigger an inflammatory response.Credit: Adobe Stock via solvod

The vagus nerve (“vagus” meaning “wandering” in Latin) consists of two nerve branches that extend from the brainstem to the chest and abdomen, where nerve fibers connect to organs. Electrical signals are constantly traveling up and down the vagus nerve, facilitating communication between the brain and other parts of the body.

Inflammation is one aspect of this back-and-forth communication. When the immune system detects an injury or attack, it automatically triggers an inflammatory response, which helps heal the wounds and repel invaders. But when not deployed properly, the inflammation can become excessive, exacerbating the initial problem and potentially contributing to disease.

In 2002, Dr. Tracey and his colleagues discovered that the nervous system plays a key role in monitoring and modifying inflammation. This happens through a process called the inflammatory reflex. Simply put, it works like this: When the nervous system senses inflammatory stimuli, it reflexively (and subconsciously) deploys electrical signals through the vagus nerve that trigger anti-inflammatory molecular processes.

In rodent experiments, Dr. Tracey and her colleagues observed that electrical signals passing through the vagus nerve control TNF, a protein that in excess causes inflammation. These electrical signals pass through the vagus nerve to the spleen. There, the electrical signals are converted into chemical signals, triggering a molecular process that ultimately produces TNF, which worsens conditions such as rheumatoid arthritis.

The incredible chain reaction of the inflammatory reflex has been observed in more detail by Dr. Tracey and colleagues through experiments on rodents. When inflammatory stimuli are detected, the nervous system sends electrical signals that pass through the vagus nerve to the spleen. There, the electrical signals are converted into chemical signals, which trigger the spleen to create a white blood cell called a T cell, which then creates a neurotransmitter called acetylcholine. Acetylcholine interacts with macrophages, which are a specific type of white blood cell that creates TNF, a protein that in excess causes inflammation. At this point, acetylcholine prompts the macrophages to stop the overproduction of TNF – or inflammation.

Experiments have shown that when a specific part of the body is inflamed, specific fibers of the vagus nerve begin to pull. Dr Tracey and his colleagues were able to map these relationships. More importantly, they were able to stimulate specific parts of the vagus nerve to “stop” the inflammation.

What’s more, clinical trials show that vagus nerve stimulation not only ‘stops’ inflammation, but also triggers the production of cells that promote healing.

“In animal experiments, we understand how it works,” Dr. Tracey said. “And now we have clinical trials showing that the human response is what is predicted by lab experiments. Numerous scientific thresholds have been crossed in the clinic and in the laboratory. We’re literally in the regulatory stages and steps, then marketing and distribution before this idea takes off.

Stimulation of the vagus nerve can already treat Crohn’s disease and other inflammatory diseases. In the future, it could also be used to treat cancer, diabetes, and depression.Credit: Adobe Stock via Maridav

Vagus nerve stimulation is currently pending approval by the U.S. Food and Drug Administration, but so far it has been shown to be safe and effective in clinical trials in humans. Dr Tracey said vagus nerve stimulation could become a common treatment for a wide range of illnesses, including cancer, Alzheimer’s disease, diabetes, hypertension, shock, depression and diabetes.

“To the extent that inflammation is the problem of disease, then stopping the inflammation or suppressing the inflammation with vagus nerve stimulation or bioelectronic approaches will be beneficial and therapeutic,” he said.

To receive vagus nerve stimulation, you would need to have an electronic device, the size of a lima bean, surgically implanted in your neck during a 30-minute procedure. A few weeks later, you were visiting, say, your rheumatologist, who would activate the device and determine the correct dosage. The stimulation would take a few minutes each day and would probably be imperceptible.

But the most revolutionary aspect of bioelectronic medicine, according to Dr. Tracey, is that approaches such as vagus nerve stimulation would not have harmful and potentially fatal side effects, as many pharmaceutical drugs currently do.

“A device on a nerve will not have systemic side effects on the body like taking a steroid,” said Dr. Tracey. “It’s a powerful concept that, frankly, scientists fully accept – it’s actually quite astonishing. But the idea of ​​putting this into practice is going to take another 10 or 20 years, as it is difficult for doctors, who have spent their lives writing prescriptions for pills or injections, that a computer chip can replace the drug. .

But patients could also play a role in advancing bioelectronic medicine.

“There is a huge demand in this cohort of patients for something better than what they are currently taking,” said Dr. Tracey. “Patients don’t want to take a drug with a black box warning, costs $ 100,000 a year, and works half the time.”

Michael Dowling, President and CEO of Northwell Health, explained:

“Why would patients continue on a drug regimen when they could go for a few electronic pulses?” Is it possible that treatments like this, pulse-driven via electronic devices, may replace some drugs in the years to come as the preferred treatments? Tracey thinks so, and maybe that’s why the pharmaceutical industry is following her work so closely.

In the long term, bioelectronic approaches are unlikely to completely replace pharmaceutical drugs, but they could replace many, or at least be used as additional treatments.

Dr. Tracey is optimistic about the future of the field.

“This will spawn a huge new industry that will rival the pharmaceutical industry over the next 50 years,” he said. “It’s not just a start-up industry anymore. […] It will be very interesting to see the explosive growth that will take place. “


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