“No prescriptions, no medicines and injections. That is the future”: Dr Kevin Tracey of the Feinstein Institute at Manhasset, NY.

The pacemaker is a device put in the body to regulate heartbeat. The stent is a device that helps smooth blood flow, likewise, can an external device be inserted into the body to control inflammation and related disorders such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), Crohn’s disease or sepsis ? This question has been pursued by doctors and scientists for a while and the solution appears on the horizon. A leader in this pursuit is Dr Kevin Tracey of the Feinstein Institute at Manhasset, NY, U.S., who wishes to “ program the body to head” using controlled electric stimulation. The science writer Michael Behar summarises Tracey’s work in the May 25, 2014 issue of New York Times Sunday Magazine, and here is a summary of his summary.

Inflammation of the body tissue happens as a response to injury, infection or immunological disorders. Inflammation has long been a black box. Treatment for this has also been not quite satisfactory. Tracey has long been studying the biochemical aspects of inflammation, and was able to isolate a molecule called TNF-alpha, which is invariably associated with the inflammatory process, indeed the cause of it. Removing it, or reducing its level from the site using antibodies and other chemicals has long been the mainstay of treatment for inflammatory diseases such as rheumatoid arthritis (RA), inflammatory bowel syndrome (IBS), Crohn’s disease, and sepsis.

While studying several components that could bring the TNF-alpha levels (and thus inflammation) down, it was discovered that the molecule acetylcholine was quite active and successful. Now acetylcholine is a signal molecule associated with the neural system — nerves and the brain. This raised the question of how a nerve-related chemical cuts down inflammation.

It was at this time that Dr Linda Watkins at the University of Colorado came out with the connection between the nervous system and the immune system. She showed that the vagus nerve (whose centre is in the back of the neck) sends signals to the brain to induce fever.

This information plus the fact that the neurochemical acetylcholine cuts down TNF alpha levels offered Tracey the idea that stimulating the vagus nerve through electric signals might cut inflammation through the release of acetylcholine, and that it could well be a method to treat RA,IBD, Crohn’s disease and sepsis.

Triggered by this “eureka moment” Tracey experimented on rats. He first cut an incision in the rat’s neck, inserted a stimulator and delivered several one-second pulses, which should release acetylcholine. Next he administered a toxin molecule which should normally cause inflammation through the release of TNF alpha. Lo and behold, the rat did not display any inflammation-based discomfort; on the other hand, a control rat which was not so electric pulsed showed all symptoms of inflammatory discomfort. What then the experiment showed was that electrical stimulation of the nervous system regulates the inflammatory response. This is analogous to regulating the heartbeat through a cardiac pacemaker. The idea of a bioelectronic treatment of inflammation by disorders was born, one that could perhaps replace treatment with drugs like steroids and antibodies.

The next step was human trials. Tracey persuaded a group in Amsterdam, Holland to recruit human patients for clinical trials. Each patient was inserted a dollar coin - shaped device to place a tiny pulse generator which had its own battery and a microprocessor in control and discharge tiny electric shocks for a minute each time, four times a day. And the patients found this treatment effective. An RA patient’s “swollen joints shrank, and blood tests that checked for inflammatory markers showed striking decline” writes Michael Behar, who titled his article in the magazine “programming the body to heal”.

Programming means generating an algorithm and a set of pulses, each suited for a given immune-related disorder. It also means to miniaturise the device so that it fits on the surface of the vagus nerve, properly insulated and containing a programmable microcircuit, a battery to power the device — all this inside the body. The command can of course be given using a bluetooth connection from the outside. One also needs to design methods that tell apart neural signals from a healthy individual from those from a patient.

All these attempts are currently under way, by a team of interdisciplinary experts — medicos, computer programmers, device makers and others. As the prototype worked, the excitement is to improve and produce patient-specific and programmable inserts, hopefully within next 10 years. But what is exciting is that treatment for inflammation-related disorders will be bioelectronic devices; “no prescriptions, no medicines, and no injections. That is the future”.

Potential downside

But, there is a potential downside, and that is malignant hacking of the software in much the same way it is done today on the software on cell phones. Professors Niraj Jha and Anand Raghunathan, both of Purdue University, say that work should start already on such “wireless protection” well ahead of time.

D. BALASUBRAMANIAN

dbala@lvpei.org

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