A small study published in the July issue of Proceedings of the National Academy of Sciences (PNAS), showed that the delivery of electrical stimulation to the vagus nerve significantly improved measures of disease activity in patients with rheumatoid arthritis (RA). RA is a chronic inflammatory disease that affects 1.3 million people in the United States and costs tens of billions of dollars annually to treat.
The publication, titled “Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis,” highlights a human study designed to reduce symptoms of RA, cytokine levels and inflammation by stimulating the vagus nerve with a small implanted device, which manufacturer, SetPoint Medical, calls a bioelectric device.
Seventeen patients with RA participated in the study. Seven were in the early stages of RA and had not responded to methotrexate. The others had more advanced disease and no improvements after taking biologic drugs.
Six weeks after being implanted, most patients noted improvement with 71.4 percent having at least a 20 percent improvement in their symptoms. In the group with early-stage RA, 57.1 percent had at least a 50 percent improvement. For the latter group with more advanced presentation of RA, 28.6 percent had at least a 50 percent improvement.
“This is the first study to evaluate whether stimulating the inflammatory reflex directly with an implanted electronic device can treat RA in humans,” said Professor Paul-Peter Tak, MD, PhD, FMedSci, the international principal investigator and lead author of the paper at the Division of Clinical Immunology & Rheumatology of the Academic Medical Center/University of Amsterdam.
“We have previously shown that targeting the inflammatory reflex may reduce inflammation in animal models and in vitro models of RA. The direct correlation between vagus nerve stimulation and the suppression of several key cytokines like TNF as well as reduced RA signs and symptoms demonstrates proof of mechanism, which might be relevant for other immune-mediated inflammatory diseases as well,” Dr. Tak added.
“This is a real breakthrough in our ability to help people suffering from inflammatory diseases,” said co-author Kevin J. Tracey, MD, president and CEO of the Feinstein Institute for Medical Research, discoverer of the inflammatory reflex and co-founder of SetPoint Medical.
“While we’ve previously studied animal models of inflammation, until now we had no proof that electrical stimulation of the vagus nerve can indeed inhibit cytokine production and reduce disease severity in humans. I believe this study will change the way we see modern medicine, helping us understand that our nerves can, with a little help, make the drugs that we need to help our body heal itself,” Dr. Tracey added.
The bioelectric device is surgically implanted in the body and delivers doses of electrical current to the vagus nerve. These electrical signals that travel through the vagus nerve and splenic nerve trigger reduction in activation of T Cells and microphages in the spleen. This results in a reduced production of systemic inflammatory mediators and reduced activation of circulating immune cells. The result is decreased inflammation, decreased joint damage and reduction in joint pain.
According to SetPoint Medical, co-founder Kevin Tracey and his colleagues discovered and characterized the Inflammatory Reflex, which is a neurophysiological mechanism that regulates the body’s immune system. The Inflammatory Reflex senses infection, tissue injury and inflammation and relays this information to the central nervous system, which then reflexively increases neural signaling peripherally through the vagus nerve and splenic nerve that extensively innervate the spleen and other visceral organs. The signal is transmitted to a novel population of T cells in the spleen, which in turn direct effector cells including monocytes and macrophages to reduce their production of the mediators that initiate and perpetuate inflammation.
Dr. Tracey published his findings in Nature in May 2000. Since then, the Inflammatory Reflex has been characterized by his group and others in more than 100 peer-reviewed papers in leading scientific journals, exploring the potential of activating the Inflammatory Reflex to alleviate inflammation.
The Wall Street Journal reports that SetPoint Medical plans broader human studies in the next six to nine months.