Four times a day, 29-year-old Kelly Owens holds a magnet over her chest, activating an implanted device that sends gentle electrical pulses up to a large group of nerve fibers in her neck. It makes her voice a little shaky while the stimulation is on. But that’s nothing compared to the pain she’s used to enduring.
Owens has Crohn’s disease, a condition that causes inflammation in the digestive tract. For Owens, the disease has been debilitating, causing pain not only in her gut, but also throughout her body.
She is one of 16 Crohn’s sufferers who have enrolled in an experimental trial in Europe where they receive electrical stimulation in an attempt to improve their symptoms. The therapy is part of a burgeoning branch of medicine called electroceuticals, or bioelectronic medicine.
The technique harnesses the fact that the human nervous system communicates in the language of electrical impulses. By hacking into that system with artificial impulses, researchers can change, and possibly correct, faulty, disease-causing communication.
Over the last decade, researchers have increasingly looked to electroceuticals to do what drugs and therapy traditionally do: improve memory, improve organ function, correct speech, treat vertigo, treat Parkinson’s disease, alleviate depression, and even restore feeling and motion after paralysis.
In the ongoing Crohn’s trial, scientists are tapping into the language of the vagus nerve, which connects the brain to several organ systems, including the gut. There are about 100,000 nerve fibers in the vagus nerve at the level of the neck. By stimulating a subset of those fibers, a signal can be sent down to the spleen. There, a series of biological actions leads to a reduction in a particular inflammatory protein, called tumor necrosis factor alpha. When the presence of that protein is reduced, patients tend to get better, the early-stage research shows.
The vagus nerve can be stimulated non-invasively through the skin or with a surgical implant. In the Crohn’s trial in which Owens participated, each subject gets a pulse generator about the size of a pacemaker implanted in his or her chest cavity just under the collarbone. The device sends the stimulation through a lead to electrodes that are surgically placed on the vagus nerve in the neck.
The study is being conducted by SetPoint Medical, a start-up in Santa Clarita, California. The technique is based on work by Kevin Tracey, president of the Feinstein Institute for Medical Research in Manhasset, New York. He and his colleagues are credited with discovering the effect of vagus nerve stimulation on inflammatory diseases and the immune system.
So far, the trial is going well, according to SetPoint, which this week released preliminary results. Of the 16 people who participated, half of the them experienced clinically meaningful improvements in typical Crohn’s disease symptoms—the kind of improvements that will enable them to leave the house, be in less pain, and avoid hospitalizations, according to SetPoint. Four of the subjects experienced remission, meaning they had minimal residual disease.
Owens appears to be one of those four in remission. (A SetPoint spokesperson would not confirm this, and said the company cannot comment on specific patients). Owens told her story today at a bioelectronic medicine symposium in Stockholm, Sweden, hosted by Feinstein and the Karolinska Institutet.
In a heartfelt speech, Owens, who grew up in New Jersey, described how her symptoms started at age 13, with inflammatory arthritis in her ankle. Over the next few years, the pain spread to her other ankle, up to her knees and eventually all the way to her arms. She developed digestive problems, heart complications, and deep ulcers on her skin known as pyoderma gangrenosum.
“I went very quickly from being an athletic kid to feeling like a 90-year-old woman,” she said in an interview with Spectrum. “It was hard to relate to other kids who were going through more age-appropriate things.”
Her doctors gave her anti-inflammatory drugs, immunosuppressants, steroids—“every drug under the sun,” she says—but none worked. By her mid 20s, she couldn’t walk a couple of blocks without stopping on a bench to rest. Every movement was painful. She had to quit her job as a high school English teacher. She developed osteoporosis as a side effect of taking the steroid prednisone.
So, when the opportunity arose to enroll in SetPoint’s experimental trial, Owens jumped at it. She had read about vagus nerve stimulation previously. SetPoint had conducted a small trial in Europe using the same stimulation treatment for people with rheumatoid arthritis—another kind of inflammatory disorder—and reported a successful outcome. Owens had a good feeling that the same treatment could work for her disease.
SetPoint’s Crohn’s study is taking place in five different locations in Europe. Owens was assigned to the Academic Medical Center in Amsterdam. When she arrived, she had to get around the city in a wheelchair.
A surgeon implanted her device on June 22, 2017, she says. Stimulation started two weeks later. Two weeks after that “I was running from train to train to make my appointments,” said Owens in the interview with Spectrum. “I remember one time my husband and I were late for an appointment at the Academic Medical Center, and I ran up two flights of stairs and got to the top and didn’t see my husband anywhere. I looked down to the bottom of the stairs and he’s standing there with his mouth open, shocked at what I had just done.”
Now, a year since her surgery, Owens says she runs, does weight training, exercises on the elliptical, and has no more Crohn’s symptoms. “It’s just gone,” she says. “I don’t have pain or swelling. I’m able to eat regular foods. A salad used to destroy my stomach and now I live on salad.” She still has osteoporosis, but hopes that will improve too with calcium supplements.
Owens will continue the stimulation for the foreseeble future. The implant in her chest will likely last about a decade before it needs to be replaced, she says.
Owens’ story is just one anecdote to emerge at the beginning of what will surely be a long road of clinical research. Larger, randomized studies, with far more subjects, will be needed before anyone can draw conclusions about the effectiveness of vagus nerve stimulation on inflammatory diseases.
There has been at least one other study of vagus nerve stimulation on Crohn’s suffers. Bruno Bonaz at Clinique Universitaire d'Hépato‐Gastroentérologie in Grenoble, France, in 2016 reported positive results in a small trial. Most of the people from that study are still in disease remission, Bonaz said in an email to Spectrum.
And SetPoint in December announced it would begin a U.S.-based rheumatoid arthritis study, this one employing a miniaturized, more advanced stimulation device, says Bill Calle, vice president of product development at SetPoint. For the Crohn’s and previous rheumatoid arthritis trials, the company used an off-the-shelf stimulator developed Cyberonics (now LivaNova) that was designed for the treatment of epilepsy and depression.
The new one, engineered by SetPoint, integrates all of the elements of the old stimulator into one pill-sized implant that gets anchored to the vagus nerve in the neck. It requires no lead, and no chest cavity implant.
And it’s programmable, so turning it on with a magnet won’t be necessary. All patients will have to do is recharge it wirelessly by periodically wearing an external collar around the neck, Calle says.
For Owens, now it’s time to pick up where she left off. She wants to go back to work, and looks forward to living like a healthy young woman, she says. The difference between her and most people her age: She already knows what it’s like to feel old. Reflecting on the last 15 years, she said: “It’s kind of a blessing to have a disease happen at an early age because you get to appreciate things in life that most people don’t appreciate until they’re much older. It’s a wonderful thing to learn those lessons at a young age.”