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Noninvasive ultrasound stimulation of spleen could lead to new treatments for inflammatory arthritis

March 14, 2019

Researchers at the University of Minnesota, in collaboration with researchers at Medtronic, have shown that noninvasive daily ultrasound stimulation of the spleen in mice with inflammatory arthritis resulted in significantly less joint swelling compared to arthritic mice that were not treated. The research is a first step to developing new treatment options for more than a million people in the United States who currently suffer from rheumatoid arthritis.

The research is currently published in Nature Communications and has resulted in a University of Minnesota-led preliminary human clinical trial.

"What we found in our mouse study is that we could actually 'turn down' the inflammatory response with daily ultrasound stimulation of the spleen from outside the body," said Daniel Zachs, the first author of the study and a biomedical engineering researcher in the University of Minnesota's College of Science and Engineering. "We're hopeful that this type of noninvasive treatment could someday supplement current treatments for people with rheumatoid arthritis."

Inflammatory arthritis is an autoimmune disease, which means that the body's immune system attacks healthy tissue in addition to germs, viruses and other foreign substances. This reaction can cause pain, stiffness, and joint damage. Current treatments usually include medicines that have a wide variety of side effects.

Researchers involved in this new study induced inflammatory arthritis in laboratory mice and then targeted the spleen with ultrasound stimulation for seven days following the injection. Some mice were treated only after the arthritis was evident on the third day. The mice that received the ultrasound treatment had significantly less joint swelling than arthritic mice that did not receive ultrasound stimulation.

"Using noninvasive ultrasound stimulation of the spleen to treat a progressive disease like inflammatory arthritis seemed like a far-fetched idea," said Hubert Lim, Ph.D., a senior author of the study and a University of Minnesota biomedical engineering associate professor in the College of Science and Engineering and the Medical School. "We were pleasantly surprised with our results and how a separate study, independently performed by GE Research and The Feinstein Institute for Medical Research published in the same issue of Nature Communications, showed findings that were consistent with our research."

In addition to focusing on reducing inflammation, the researchers also studied the specific type of white blood cells that were required for reducing inflammation. By analyzing gene expression and deleting specific types of white blood cells, the researchers found that white blood cells called T cells and B cells were both involved in reducing the severity of arthritis.

"Rheumatoid arthritis can be a devasting disease if not treated aggressively," said Bryce Binstadt, M.D., Ph.D., a senior author of the study and an associate professor of Pediatrics in the Division of Pediatric Rheumatology in the University of Minnesota Medical School. "The idea that we can improve arthritis treatment by using ultrasound rather than additional medications is exciting. This research shows the progress we can make when doctors and engineers come together to solve problems."
-end-
In addition to Zachs, Lim, and Binstadt, the research team included Jamu Alford, Sarah Offutt, Yohan Kim, and Jerel Mueller from the Restorative Therapies Group at Medtronic; Claire Kaiser, Abigail Heiller, and Hongsun Guo from the University of Minnesota Department of Biomedical Engineering; and Rachel Graham, Jennifer Auger, Nathaniel Schuldt, Raini Dutta from the University of Minnesota Center for Immunology and Department of Pediatrics.

This research was primarily funded by the United States Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense.

To read the research study entitled "Noninvasive ultrasound stimulation of the spleen to treat inflammatory arthritis," visit the Nature Communications website.

University of Minnesota

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