Neuromodulation of Inflammation and the Immune System

In recent years, neuromodulation research has revealed the complex bidirectional interaction between the nervous system and immune system. The discovery of this neural-immune system has ignited a new field of neuromodulation targeting peripheral nerves and end-organs for treating a myriad of diseases.
Ultrasonic Modulation of Chronic Inflammation

We are investigating noninvasive neuromodulation of the peripheral nervous system using focused ultrasound to treat chronic inflammation, initially in a transgenic mouse model of rheumatoid arthritis. Ultrasound energy is targeted to the spleen and splenic nerve, which communicate directly with leukocytes. We have found that the severity of arthritis can be reduced using specific ultrasound stimulation parameters, and are currently investigating which cytokines and cellular pathways are involved in the anti-inflammatory effect. We also plan to incorporate ultrasound imaging for real-time visualization and targeting of the spleen during neuromodulation, as well as monitoring disease progression by imaging joint and muscle inflammation.
Clinical Trial: Ultrasonic Treatment for Rheumatoid Arthritis
Based on encouraging animal data, we are initiating a clinical trial translating our peripheral nerve and animal studies to the treatment of rheumatoid arthritis in human patients. Noninvasive ultrasound will be applied to the spleen in patients suffering from rheumatoid arthritis and outcomes will be assessed via cytokine analyses, Disease Activity Score 28-CRP (DAS 28-CRP) and imaging techniques. The long-term goal is to develop a wearable ultrasound device that can image and localize the target cells and apply stimulation to those cells for treating rheumatoid arthritis or other autoimmune disorders.
Funding: DARPA
Collaborators: Sarah Offutt, PhD (Medtronic); Bryce Binstadt, MD, PhD (Pediatric Rheumatology, University of Minnesota); Erik Peterson, MD (Rheumatic and Autoimmune Diseases, University of Minnesota)