Can bioelectronics help supersede the use of traditional drugs?

Tapping into the neural connections between the brain and the body’s organs may hold the answer to fighting diseases sans drugs.

• Image 1 Vagus nerve stimulation (VNS). Photo credit: Mayo clinic health library.

The vagus nerve is comprised of 90% afferent, i.e., sensory nerve fibers, and plays a central role in transmitting information about the functional status of various organs to the brain¹. This role also entails the monitoring of the body’s inflammatory processes: When microbial infections occur, the immune cells release pro-inflammatory signals - an accumulation of which can result in systemic inflammation. The vagus nerve thus alerts the brain when there is an excess of molecules such as cytokines. The brain, now notified of a potent infection, reflexively triggers the release of anti-inflammatory substances to avert harmful inflammation². A serendipitous electrical stimulation of the vagus nerve helped decipher that this attenuation occurs via the efferent fibers that make up the reminder of the vagus nerve. It was thus demonstrated for the first time that the brain can regulate the levels of the Tumor necrosis factor (TNF) via the vagus nerve – a mechanism termed cholinergic anti-inflammatory pathway³.

Electrically stimulating the vagus nerve using pacemaker-like devices to tackle seizures in epileptic patients has been in practice since the 1990’s, and so has been the treatment of depression with vagal nerve stimulation (VNS). These procedures have relied on the fact that the vagus nerve serves as a portal to the brain stem; thus, psychiatric diseases have been the prime target of VNS⁴. 

With the discovery of the link between the immune system and the central nervous system (CNS), the anti-inflammatory effect of VNS has been considered a therapeutic option for TNF diseases such as rheumatoid arthritis (RA), Crohn’s disease, and endotoxemia². Animal experiments have shown VNS to be successful in treating hemorrhagic shock, ischemia, reperfusion injury, and even heat shock⁵. Further, the first clinical trial to test a newly devised nerve stimulator to treat RA (based on the cholinergic anti-inflammatory pathway) began in 2011; although suspended shortly afterwards, the trial was reopened in 2013, and is currently underway⁶. Interestingly, the VNS-immune system-CNS connection is now being explored as a potential anti-cancer strategy. The abundance of pro-inflammatory signals in tumour microenvironment, and the control of metastasis in animals through the usage of anti-inflammatory drugs targeting TNF have sparked a new hope in exploiting the brain-immune system relationship to treat cancer¹.

Thus, millions of dollars are currently being invested to dissect and interpret the signals that are transmitted between the brain and various organs, and to manipulate these signals for treating varied diseases using novel electronic devices⁷. The pacemaker-like devices, used to treat epilepsy and depression, are controlled with a simple magnet^4,8; the new generation of devices that modulate the nervous system may one day be even remotely controlled via the internet. The fear of hacking is therefore ever looming⁷. For the giant drug companies currently interested in bioelectronics there is the obvious incentive of a lucrative money-making opportunity. But will bioelectronics research ease the pressure of drug discovery and our reliance on pharmacological substances, and consistently help battle diseases? Only time can tell.

Cover image: Wikipedia.

References

1. http://www3.imperial.ac.uk/bioinspiredtechnology/research/neuralimmunity

2. Tracey, K. et al., Mind over immunity,The FASB Journal (2001). doi: 10.1096/fj.01-0148hyp

3. Borovikova, L. et. al., Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin, Nature (2000). doi: 10.1038/35013070

4. George, M. et. al., Vagus nerve stimulation: a new tool for brain research and therapy, Biological Psychiatry (2000). doi: 10.1016/S0006-3223(99)00308-X

5. Yamakawa, K. et. al. Electrical Vagus Nerve Stimulation Attenuates Systemic Inflammation and Improves Survival in a Rat Heatstroke Model, PLosOne 2013. doi: 10.1371/journal.pone.0056728

6. http://www.clinicaltrials.gov/ct2/show/NCT01552941 

7. http://www.nytimes.com/2014/05/25/magazine/can-the-nervous-system-be-hacked.html?hpw&rref=magazine&_r=1

8. http://www.webmd.com/depression/vagus-nerve-stimulation

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