An Accidental Cure for Inflammatory Diseases

An accidental discovery within a Long Island, N.Y., health system has led to the creation of a bioelectronic medical treatment for inflammatory diseases.

The still-experimental treatment involves implanting a small device that would transmit electrical pulses in the nerves. If proven safe and effective, the discovery could transform patient care for rheumatoid arthritis and inflammatory bowel disease. The implantable devices also could eat into the costs of treating various diseases, which in the case of rheumatoid arthritis, has been estimated to total $22 billion per year.

“Identifying the exact role of the different nerve bundles in the inflammatory reflex bolsters our understanding of the relationship between the central nervous system and the vagus nerve,” said Kevin J. Tracey, M.D., president/CEO of the Feinstein Institute for Medical Research and the scientist who made the discovery. “Furthermore, we now know that stimulating the vagus nerve for as little as half a millisecond is enough to inhibit tumor necrosis factor (TNF) production.”

Working at the institute, part of the North Shore-LIJ Health System, Tracey’s neurological research on the human brain unexpectedly led in 1998 to the identification of a physiological relationship between the brain and the body that previously was unknown. The nervous system is hardwired to the immune system, and the brain is in control, Tracey told Hospitals & Health Networks. After establishing the neural bundles activated in vagus nerve stimulation, the researchers found that only low-intensity, short-duration, electric pulses were needed to reduce the production of inflammation-inducing cytokines. Repetition of the pulses did not increase the success of the treatment in this experiment indicating that a single stimulating pulse is potentially sufficient.

Thus, with rheumatoid arthritis, the brain likely is sending electrical impulses that activate the immune system improperly or unnecessarily—for reasons unknown—leading to the disease’s trademark swollen joints. A possible treatment would involve electronically telling the spleen to not cause the inflammation.

Such a treatment currently is being commercialized by a company Tracey co-founded called SetPoint Medical. Its scientists have shown some success in implanting devices that manipulate those electrical signals to prevent or limit the inflammation for rheumatoid arthritis. Clinical trials began last year to treat inflammatory bowel disease — the first round with humans involved eight patients, two of whom experienced remission from rheumatoid arthritis and six of whom had a positive response, according to SetPoint executives.

An alternative to drug therapy would be welcome for the 1.3 million Americans suffering from rheumatoid arthritis, a condition affecting the joint lining that causes a painful swelling which eventually can result in bone erosion and joint deformity. Current biologic medicines to treat the disease can lead to skin reactions at the site of injection, and can increase the risk of all types of infections, including tuberculosis, according to the American College of Rheumatology.

GBI Research estimated in a report that the cost of treating rheumatoid arthritis in the United States would climb to $9.3 billion per year in 2020 from $6.4 billion in 2013. At the same time, the number of people with the disease is expected to rise to 1.68 million by 2020.

Before any savings can be reaped, however, researchers must prove the technology works and is safe. And while the field of neuromodulation has existed for years, its application has been limited to procedures in which little is understood about the mechanics, Christopher Czura, vice president of scientific affairs at Feinstein, told HHN.

The medical community has long been aware that pain can be relieved by blocking nerve conduction, and that stimulating the brain can relieve symptoms of Parkinson’s disease. But the reasons they work have mostly remained a mystery. In bioelectronic medicine, a subset of neuromodulation, the reason is crucial. “We bring the pharmaceutical rigor of drug development to the concept of stimulating nerves to treat disease,” Czura said. “We understand the full molecular pathway of why it works.”

The federal government also aims to expand knowledge in neuromodulation. The National Institutes of Health has committed $240 million over six years to encourage different scientific communities to collaborate, focusing first on the reasons an approach might work before asking if it would work.

Given the complicated nature of the nervous system, gaining the desired understanding will take time. The vagus nerve, a major area of focus, runs from the brain and has 80,000 to 100,000 nerve fibers. “The idea going forward will be to have extremely precise, extremely small electrodesthat can stimulate a few nerve fibers at a time,” Tracey said.

SetPoint’s research involves the use of a modified stimulator that originally was designed to treat depression and epilepsy. The epilepsy version of the device pulses for about 30 seconds, every five minutes, around the clock, Czura noted.

SetPoint recalibrated the device to run in the rheumatoid arthritis trial for just 30 seconds once a day, and that has shown to be enough to work, HHN reported. In addition to the implantable nerve regulator, the treatment requires a wireless charger and an Apple iPad prescription app. Late last year, the company announced it was launching a similar trial to treat Crohn’s disease, an inflammatory bowel disease.

“Seeing successful results with low-level electrical current is a significant finding,” said Yaakov Levine, Ph.D., senior research scientist at SetPoint Medical. “This indicates the potential for limited side effects, as well as promise for device miniaturization, both of which will be important to bringing vagus nerve stimulation into the mainstream.”