Kelly Owens was a medical mystery, her teens and 20s being plagued by a cascade of seemingly unrelated health problems that left her debilitated. For a decade and a half, she was given drug after drug—22 in all—with little effect. Then she saved Strom.
“I couldn’t even remember how ‘healthy’ I felt since it was 15 years ago,” says Ms. Owens, 33. Now she and her husband are talking about having a child, something they do for had held impossible. She credits Kevin Tracey, an innovative neurosurgeon she found through Facebook.
Ms Owens was an athletic 13-year-old when she sprained her ankle while tap dancing. A few weeks later, her ankle was still swollen and she developed severe nausea and diarrhea. A year or two later her other ankle swelled up, although she never injured it. Then her knees became infected.
After a colonoscopy and endoscopy, she was diagnosed with Crohn’s disease, an inflammatory bowel disease. Blood tests and a physical exam revealed spondyloarthropathy arthritis affecting her spine, joints and organs. She developed blood clots and skin ulcers. When she graduated from college, she says, there wasn’t a joint in her body that didn’t hurt. Her myriad ailments made it difficult for her to walk and forced her to quit her job as a teacher. To control her joint inflammation, she was prescribed steroids that left her bones as brittle as those of a 70-year-old woman.
She was 25 when she saw a Facebook video of Dr. Tracey, CEO of the Feinstein Institute for Medical Research in Manhasset, NY, stumbled upon discussing how electricity could replace drugs. dr Tracey, 64, pioneered research showing that electrical stimulation of the vagus nerve — the nervous system’s “main circuit board,” which originates in the neck and connects the brain to the rest of the body — could suppress chronic inflammation in diseases like Crohn’s disease and Rheumatoid arthritis.
She enrolled in a vagus nerve stimulation study by SetPoint Medical, a California biotech startup that Dr. Tracey co-founded in 2007. With financial help from family and friends, she and her husband relocated to Amsterdam, one of the locations where the trial took place. The study’s lead investigator was Geert D’Haens, a global expert in inflammatory bowel disease at Amsterdam University Medical Center.
SetPoint implanted a pacemaker-sized device in her chest cavity that sends stimulation to electrodes surgically placed on her vagus nerve. Her symptoms began to improve within weeks. Soon she could not only walk, but also walk. Two months after implanting the device, doctors found her in clinical remission. Her ailments have been kept in check and her doctors have weaned her off steroids.
Scientists have long known that the vagus nerve transmits signals between the brain and internal organs that regulate physiological processes such as digestion, breathing, and heart rate. For example, when you exercise, your heart speeds up. Then your brain sends a signal through the vagus nerve, telling your heart to slow down so it doesn’t beat out of control.
dr Tracey’s breakthrough two decades ago was the discovery that the brain also controls the immune system via the vagus nerve. By using electrical stimulation to hack neural networks, it’s possible to regulate the immune response and perhaps one day cure inflammatory diseases like multiple sclerosis, lupus, and even Alzheimer’s disease.
The story of this novel discovery begins with Dr. Tracey’s painful childhood. His mother died of an inoperable brain tumor when he was 5 years old. This sparked his interest in neurosurgery. He wanted to develop treatments so that other children would not suffer as he and his two younger siblings did. He attended medical school and joined a New York City hospital as a resident of neurosurgery.
In 1985, he was taking care of an 11-month-old girl named Janice. “She had crawled across the kitchen floor while her grandmother was cooking dinner. And Grandma turned to drain boiling water into the sink and spilled the boiling water on her granddaughter,” recalls Dr. Tracey. “We didn’t think she would survive. But she did – she survived a month – and then inexplicably went into shock and died in my arms. And so I was haunted by her death. She died of septic shock.”
Septic shock occurs when a nonfatal injury or infection leads to organ failure and dangerously low blood pressure. Sepsis causes 1 in 5 deaths worldwide. In 1985, scientists did not understand what causes the disease. Janice’s death spurred Dr. Tracey to research the biology of sepsis: “What we discovered is that the molecule that killed Janice was made by her own immune system. It is a molecule that is now known as TNF – tumor necrosis factor.
TNF is a cytokine, a protein made by the immune system to send signals that can cause or reduce inflammation. But the discovery of TNF only explained part of the mystery behind sepsis. Questions remained, said Dr. Tracey: What controls the amount of cytokines produced? Why do some people, like Janice, produce massive amounts of cytokines that can kill them?”
While testing an experimental drug that blocked TNF production in mice suffering from stroke, his lab stumbled upon a lead. Not only did the drug block TNF production in the rodents’ brains, which helped cure the strokes; it also turned off TNF and other cytokines produced in the rest of the body. This led to the discovery that “the brain communicates with these organs by sending signals through the vagus nerve.”
His lab performed two more experiments on mice that confirmed this hypothesis. “So now we knew that the vagus nerve can pass this off switch on to the immune system.” He postulated: “If there is an off switch in the vagus nerve, there must also be an on switch, that’s how a reflex works.” Further experiments and research confirmed this his guess.
In the case of sepsis, bacteria activate white blood cells to produce cytokines that can help heal wounds. An inflammatory condition like Ms. Owens’ can also trigger the release of cytokines. Problems arise when the nervous system cannot regulate the production of cytokines. “If the nervous system doesn’t control this response, the immune system can overproduce cytokines,” which can lead to autoimmune diseases like rheumatoid arthritis and Crohn’s disease, says Dr. Tracey. Hence the treatment: “You can implant a device in the vagus nerve of humans or animals, and by controlling the activity of the nerve with the nerve stimulator device, you can control the magnitude of the cytokine response.”
The vagus nerve is actually a network of about 160,000 nerve fibers, 80,000 on either side of the neck. Each fiber has a specific task – for example, controlling the heart rate. These fibers also provide information to the brain, which processes it and sends signals back through the vagus nerve or to nearby structures like the pituitary gland, which regulates hormone production.
How do the doctors know the Fiber or fibers to be stimulated? dr Tracey explains a “cool trick called optogenetics” in which mice are genetically engineered to stimulate fibers in their brainstem to send signals to the body when activated by a laser beam. The researchers can then find out which fibers control which processes by directing a laser at the neurons.
More than 100 studies are being conducted worldwide using vagus nerve stimulation for a range of conditions. SetPoint conducted three small studies of vagus nerve stimulation in rheumatoid arthritis and Crohn’s disease. “The same device implanted in the same place can be used for other diseases,” says CEO Murthy Simhambhatla. (Dr. Tracey resigned from the company’s board of directors in 2011 to spend more time in his laboratory after meeting the first rheumatoid arthritis patient treated in a SetPoint clinical trial and experiencing a complete remission. He works continues as a consultant to SetPoint.)
Eight of the 16 patients in Ms Owens’ study showed improvement after four months, and she and three others went into complete remission. SetPoint plans to conduct larger randomized controlled trials in patients who have failed to respond to biologic drugs. Such studies can take many years to complete, as is the case with pharmaceuticals, but the Food and Drug Administration has been helpful in supporting the innovation. Last year, the FDA approved the technique to help people who have suffered motor damage from stroke.
Vagus nerve stimulation could also help some people suffering from ‘Long Covid’, says Dr. Tracey, although he cautions that more research is needed. A study earlier this year found that most patients with long-term Covid-19 illness had signs suggestive of vagus nerve dysfunction, including diarrhoea, dizziness and a rapid heart rate. Many also showed evidence of vagus nerve damage on medical imaging.
Some patients may shudder at the thought of having a device implanted that sends electrical impulses to their brain and back to their body. “Some were quick to say, well, vagus nerve stimulation is invasive,” says Dr. Tracey. “Well, I would say that biologics are also invasive. They’re administered with needles.” He adds that the roughly 150,000 epilepsy patients who have been treated with vagus nerve stimulation over the decades have had very few side effects.
Some drugs also work by chemically stimulating the vagus nerve and may have the potential to treat conditions other than those for which they were originally developed. dr Tracey conducted a small study that found that famotidine (also known by the brand name Pepcid) can shorten the duration of acute Covid in patients with mild to moderate symptoms by activating the vagus nerve and suppressing the cytokine storm.
Healthy behaviors like exercise and meditation can also stimulate the vagus nerve, says Dr. Tracey, but they may not help patients who have damaged nerve fibers or who have a genetic condition. The latter may have caused Ms Owens’ complaints.
dr Tracey is reluctant to say she’s cured: ‘She could be. We do not know it. How do you know if she’s cured? No one wants to turn off the device.” But she feels like a normal, healthy 33-year-old and hopes her story will inspire others with similar conditions: “Patients really need to have hope.”
Ms. Finley is a member of the Journal’s editorial board.
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