1. References

2. Bioelectronic Medicine

This article is about the science or practice of using of precise electrical pulses to treat the underlying pathophysiology of chronic diseases.

1. What is Bioelectronic Medicine?

a. Bioelectronic medicine is a new approach to treat disease and injury using electrical pulses instead of drugs. All major organs of the body are innervated, allowing the brain to both monitor and regulate organ function. Bioelectronic medicine uses device technology to read and modulate the physiological activity by leveraging electrical activity within the nervous system, opening new doors to real-time diagnostics and treatment options for patients. |url=https://www.feinsteininstitute.org/programs-researchers/bioelectronic-medicine/what-is-bioelectronic-medicine/}} Nerve-stimulating devices have the potential to modulate specific nerve activity, elicit a specific change in function of the organ that the nerve innervates, and restore health, without the complicated side effects of pharmaceutical agents. Current treatment methods focus on utilizing small devices to generate and deliver periodic digital doses to nerve bundles to create a disease-fighting effect that can last for hours or days based on mechanisms similar to drug therapies.^[1]. Such devices are already in clinical trials to treat inflammatory diseases such as rheumatoid arthritis (RA) and inflammatory bowel disease ^[2].

2. History of Bioelectronic Medicine

a. A number of key scientific discoveries, medical advances and technological developments played a crucial foundational role in the evolution of bioelectronic medicine. The use of electrical signals to influence the human body dates back to ancient times with the first known written document on the therapeutic application in AD 46, when Scribonius Largus, a Roman physician, mentioned the use of the electrical discharge from the electric ray in his work, Compositiones Medicae, to treat gout and headache ^[3]. Following the fundamental developments of man-made electricity, electrical impulses have been developed and recorded for use in therapeutic applications including cardiac disease management since as early as the late 1800’s, starting with John Alexander MacWilliam’s publication in the British Medical Journal on his experiments with electrical impulses and the human heart through the development of the modern-day pacemaker and defibrillator. Since the 1950s, there have been many improvements to medical devices, including the advancement to wearable transistorized models and implantable technology, new lead and leadless technologies, smaller device sizes, longer battery lives, and MRI compatibility, to name a few.

b. The key differential that sets bioelectronic medicine apart from traditional neuromodulation is the biological impact it has in the body and ability to address the underlying disease by harnessing the body’s own mechanisms versus mediating or masking the symptoms ^[4]. Two primary discoveries made in this field are that inflammation plays a role in virtually all diseases and that inflammation can be modulated through a nerve in the neck called the vagus nerve. In 2002, discovery of a new biological pathway called the inflammatory reflex by Kevin Tracey, president and CEO of the Feinstein Institute for Medical Research in Manhasset, New York, and professor of Molecular Medicine and Neurosurgery at the Zucker School of Medicine, opened the door to treating disease systemically using electricity. Dr. Tracey and his colleagues identified this neural mechanism for controlling immunological responses to infection and injury when they were studying a chemical that blocked inflammation in the brain and simultaneously discovered that the same chemical decreased inflammation in the spleen and other organs. Tracey and his colleagues concluded that the brain is in constant communication with the immune system via the vagus nerve ^[5]. The vagus nerve has an important role in regulation of metabolic homeostasis, and efferent vagus nerve-mediated cholinergic signaling controls immune function and proinflammatory responses via the inflammatory reflex.

3. The Inflammatory Reflex/Vagus Nerve

a. The vagus nerve, the longest of the autonomic nervous system—which controls internal organs and glands—extends from the head to the abdomen, and has both sensory and motor functions. Its nerve fibers carry information on the workings and health of such organs such as the heart, esophagus, spleen, pharynx, larynx, and the bowels.

Researchers, with specialties in signal processing and machine learning, used the method to better understand the specific inflammatory responses associated with different diseases.

b. The vagus nerve is the longest of 12 pairs of cranial nerves that sends information from many parts of the body, such as the heart, lungs or other abdominal organs back to the brain when it detects a problem. The brain is also responsible for transmitting information through the vagus nerve back down to the organs and controlling inflammation.

Using small stimulators planted on the vagus nerve, the devices can send electrical signals to restore and reset immune-mediated inflammatory activity.

4. Clinical applications of Bioelectronic Medicine

a. Research in bioelectronic medicine is being considered more broadly for the development of applications in inflammatory diseases and conditions at large. Dr. Paul-Peter Tak, an immunologist, academic and venture partner who, based then at the University of Amsterdam’s teaching hospital, Academic Medical Centre, and having specialized in the fields of rheumatology and immunology, explored the beneficial effects of stimulating the inflammatory reflex and showed the crucial role of the alpha-7 nicotinic acetylcholine receptor in rheumatoid arthritis (RA). Dr. Tak further demonstrated that activating the inflammatory reflex with vagus nerve stimulation treated the rodent model of RA, preventing inflammation and damage to the joints. These tests and others showed not only regression of RA disease, but also a reversal in bone erosion ^[6]. Early research, published by Dr. Frieda A Koopman from University of Amsterdam’s Academic Medical Centre, noted the translation of the animal research into diseased human studies. This research was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) and demonstrated that bioelectronic medicine may be used to improve disease activity in RA patients ^[7].

b. Further tests in rodents have also demonstrated lesion reductions in laboratory models of Crohn’s disease. In addition, in a study by Bruno Bonaz, Professor of Gastroenterology in the Grenoble Faculty of Medicine and Hospital in France, and his colleagues, Crohn’s patients showed signs of clinical and biological remission, including restored vagal tone, after being administered bioelectronic medicine.

c. In 2018, Researchers at the Feinstein Institute carried out clinical trials on Lupus patients in which proprietary bioelectronic medical devices were found to reduce pain, inflammation and fatigue. Previous studies published by the institute document the results of bioelectric devices in affecting diabetes, paralysis, and inflammatory bowel disease ^[8]. In California, bioelectronic devices for use in psychiatric disorders are being investigated. Funding for development in the field is driven primarily by various foundations and venture capital funds. Efforts in the public sector from organizations such as SPARC (Stimulating Peripheral Activity to Relieve Conditions) and DARPA (Defense Advanced Projects Research Agency) also contribute to research and development of devices for neural pathways and inflammatory diseases ^[9]

References

Bioelectronic Medicine

• Mowtowr-e Ashayir Mohammad Safineh Taj
• Mowtowr-e Ashayir Shirazad
• Mowtowr-e Ashayir Shirazad 1
• Mowtowr-e Ashayir Shirazad 2
• Mowtowr-e Atahaddu
• Mowtowr-e Atahadik
• Mowtowr-e Ayisi Ayzadi
• Mowtowr-e Ayyub Borhan Zehi
• Mowtowr-e Azim Borhan Zehi
• Mowtowr-e Badal Khalqpur
• Mowtowr-e Bagh-e Baghun
• Mowtowr-e Bahram Khalqpur Chah Hasan
• Mowtowr-e Bahram Rayisi Chah Hasan
• Mowtowr-e Bajar
• Mowtowr-e Bajar, Khash
• Mowtowr-e Bakhtiar Akhlas Pur
• Mowtowr-e Baluchha
• Mowtowr-e Baluch Mohammad Jadgal
• Mowtowr-e Barnayan
• Mowtowr-e Behruz
• Mowtowr-e Beyjar Zehi
• Mowtowr-e Beyt Allahi
• Mowtowr-e Bi Barg Rigi
• Mowtowr-e Bolbol Paradel
• Mowtowr-e Bonadi