From inflammation to depression: electricity is revolutionizing medicine

During the first few days of treatment, the man reported that his symptoms of depression had decreased by more than 50%. After 22 weeks, doctors said her depression had subsided. After 37 weeks, the researchers reduced stimulation by 25% a week to zero to see if their symptoms were changing. The patient reported a constant increase in anxiety and worsening mood. When the researchers reactivated the electrodes, her symptoms disappeared again, suggesting that prolonged stimulation was responsible for improving her mood and that if she continued, she would likely remain in remission.

“He’s doing very well,” says Shet. “He leads a much fuller life. He works. His social relations are going very well.” Last year, he visited Shet’s doctoral students to help him give a lecture on depression.

Following this first report, Sheth’s team recorded and implanted therapeutic electrodes in two other patients with major depression. “We’re starting to see that our first two patients generally have slightly different patterns that predict better or worse mood,” he said, adding that he was still analyzing data from the third patient. “This precise medicine, this approach to individualization, I think will be crucial.

Signal amplification

In 2010, Chad Button, an engineer and medical researcher at the Feinstein Institute for Medical Research, experimented with electrodes implanted in the brain to help paralyzed patients regain movement. In 2019, he wondered if he could use electricity to help patients without opening their skulls.

In most cases of limb pain or tingling after accidents, the nerve or spinal cord is only partially cut off. This seemed to be the case with Sharon Laudisi’s thumb injury, which means that a small amount of electrical signal from the brain can move between the brain and the limb; it’s just not enough to ignite a sensation or start a movement.

Button and his team suspected that if they could increase the signal, they might be able to help Laudisi’s brain communicate with her thumb again. But for that, they had to map the neural connections that remained.

To determine the ideal location of the electrode patch on Sharon’s neck, the team stimulated, moved the patch, stimulated, moved the patch until they found a place that allowed the patch to communicate only with her hand and not send the wrong signals. over your body.

Stimulating the Laudisi neck patch is like increasing the volume of a speaker partially blocked by furniture. After finding the place that maximized the signals to her thumb, Sharon wore the electrode patch once a week for an hour for a total of eight weeks.

At the end of this time, Laudisi managed to generate 715% more power with his thumb. Today, his thumb is not as strong or flexible as it used to be, but he can press a pen, use keys and fasten a shirt. “I don’t think there are words to describe how impressive it is,” he said.

Bouton says he still can’t figure out what the cost of such treatment would be if approved by the FDA, but believes “it would be affordable and accessible to many people who could benefit from it.”

short circuit inflammation

When training as a surgeon, Tracy, CEO of the Feinstein Institute, cared for a child in the burn department of a New York hospital. He died in her arms. “We didn’t know what he died of,” he said. “It was disturbing.” But later, learning that he had died of sepsis, he decided to devote his future research to the disease.

He and his team discovered a protein, tumor necrosis factor (TNF), which they believe was responsible for the girl’s death. Researchers describe the role of TNF in promoting inflammation to neutralize invading pathogens such as bacteria and viruses, as well as its more sinister ability to attack the body’s own tissues. Excessive inflammation can cause sepsis, shock, and even cytokine storms, the result of overactive immune cells that can worsen diseases such as COVID-19 by damaging the very tissues the immune system is trying to protect and heal. If you can block TNF in a patient with dangerously high cytokine levels, “you can cut off the disease’s fuel,” Tracy said.

Tracy’s discoveries in the 1980s led to the development of drugs to inhibit the TNF protein and reduce inflammation. Several of these drugs, such as Enbrel and Remicade, are now used to treat autoimmune diseases in which a person’s immune system destroys its own healthy tissue.

But these drugs don’t work for all patients, so Tracy thought there might be a better way to target the inflammation. He suspected that because the autonomic nervous system reflexively controlled blood pressure, digestion, and other processes, there must be a reflex controlling inflammation. It focuses on the vagus nerve, a dense bundle of about 100,000 nerve fibers that travels from the brain, along each side of the neck, through the heart, lungs, chest and all the way to the colon.

“We found that the electrical signal in the vagus nerve is like the brake on your car. It stops the TNF system, the inflammatory system, from going wrong, ”says Tracy. Animal studies show that if the vagus nerve is severed, the damaging inflammation may increase, exacerbating autoimmune diseases.

Trey and his team have developed an implantable device less than a centimeter long that is placed in the neck and stimulates the vagus nerve, thus reducing TNF production. Early devices were attached to batteries that were implanted under the patient’s clavicle, but newer versions are the size of a small claw and can be charged by wearing a metal collar to charge once a week.

The neurons that make up the vagus nerve are involved in countless processes, Tracy explains, but the device is aimed only at those that regulate TNF because they are hypersensitive to surrounding nerve cells.

Officialtrials.gov (the official website of the US government’s clinical trials) has hundreds of clinical trials testing forms of vagus nerve stimulation to treat conditions ranging from COVID-19 to chronic pain. Some applications have more scientific support than others, Tracy said, citing recovery from stroke (for which the FDA has already approved a vagus nerve device) and inflammation control. Clinical trials conducted locally can also be found on the website of the Spanish Medicines Agency.

For other indications, he points out that scientists may not yet really understand the mechanisms. He also doubts those who claim to stimulate the nerve outside the skin instead of implanting an electrode. “How do they know what they’re doing?” He asks, stressing that researchers need to start identifying specific targets such as TNF before testing therapies.

electricity everywhere

Although scientists often believe that electrical communication takes place between neurons, Michael Levine, a biologist and computer scientist at the Wyss Institute in Boston, points out that all cells in the body communicate through electricity. Cells have channels in their membranes that open and close, allowing charged ions to flow in and out of neighboring cells, affecting how cells grow and work together. Along with molecular signals, electrical gradients between cells help signal to the developing fetus that there must be two eyes, for example, and how far they must be.

“This is really his future, the manipulation of this natural flow of information. We want to be able to program the thing with the exact currency it uses, ”says Levin.

Instead of stimulating individual cells, Levin is working to change the spatial distribution of electronic signals in different areas of the body to encourage groups of cells to work together to heal or regenerate. He compares his strategy to programming software for the body’s genetic hardware.

This means that bioelectrical treatments can go beyond stimulating individual cells with electrodes.

In frogs, for example, he and his team used computational analysis to determine the ideal electrical environment to stimulate limb regeneration. Like pop spoons, these animals can regenerate lost tissue, but when they mature, they lose most of that ability. The analysis allowed him to choose five drugs that open and close the channels of the cells to achieve the desired electrical state. After amputating the animal’s hind leg, they created a portable bioreactor with these five drugs. After only 24 hours of wearing the reactor, the animal’s limb continued to grow for 18 months. The new limb was not fully grown, but it had skin, bones, blood vessels, and nerves.

Levin explained that it will take scientists some time to understand the various electrical states that guide the activity and development of human cells. But then he believes there are few obstacles to progress. There are already many drugs that can be used in these therapies, such as those in the frog bioreactor. Scientists just need to know how and when to combine them to create the electrical environment the body may need.

Deep brain stimulation and vagus nerve stimulation are “good applications” of bioelectric medicine, Levin said. “I just want people to understand that this is the tip of the iceberg.”

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