From the ancient Egyptians’ use of electric fish to treat headaches to the invention of pacemakers to regulate heart rhythms in the 1950s, the field of bioelectronic medicine — which makes use of electrical signals instead of drugs to diagnose and treat disease — has advanced and is started to come into its own. Where is the field now? And what are the most promising opportunities for life-changing new therapies and diagnostics?
New research led by Imanuel Lerman, head of the Lerman Lab of the UC San Diego Qualcomm Institute and UC San Diego School of Medicine Department of Anesthesiology, as well as the VA Center of Excellence for Stress and Mental Health, provides some answers.
“This paper is intended to be a roadmap to the future of the biomedicine field,” Lerman said. “We’re putting a flagpole in the ground and saying, ‘This is what we’re planning to do, and this is the story behind it.’ That’s why there are 180 references. We want to make sure that everybody has the resources they may need to be able to understand and read deeper if they want to.”
The research, published today in the peer-reviewed journal Bioelectronic Medicine, was commissioned by Convergent Research, a nonprofit that addresses the need for focused, high-impact, multi-entity projects that might otherwise fall through the cracks of current funding mechanisms.
A World of Promise
Even beyond increasingly sophisticated pacemakers, bioelectronic medicine already has earned a place in modern medicine. Implantable devices have been approved by the US Food and Drug Administration for movement disorders such as Parkinson’s disease (via deep brain stimulation); back pain and injury-related motor dysfunction (via spinal cord stimulation); and instances of epilepsy, depression, stroke and migraines (via stimulation of the vagus nerve, which helps control digestion, heart rate, mood and the body’s inflammation response).
More recent developments have included noninvasive techniques, in which the nervous system can be stimulated by devices from outside of the body. Transcranial magnetic stimulation, for one, was approved for depression in 2008. Since then, its indications have expanded to include migraine-related pain, obsessive-compulsive disorder, smoking cessation and anxious depression.
Lerman and colleagues see much promise ahead.
The new paper highlights the advent of noninvasive bioelectronic techniques. Not only does this approach avoid surgery-related risks, but it also offers some distinct advantages over the pharmaceutical treatments we take for granted.
“Non-invasive neuromodulation is an emerging field where we believe there’s a big opportunity,” said Lerman, who is also a provider with UC San Diego Health. “The potential for scale is there, since a device doesn’t have to be refrigerated. It’s not a drug. All you need is electricity to run the device or a battery. And it can use the body’s own system to tamp down inflammation.”
In addition, pairing bioelectronic medical devices with sensors can create self-regulating “closed loop” systems that can adjust according to the needs of the individual. No longer tied to a standard dose of a drug, bioelectronic devices could truly provide individualized medicine continuously adjusting doses based on feedback from a patient’s biomarkers.
While much work is still required to create such closed-loop systems, Lerman and colleagues see them as a potentially transformative approach to medical treatments.
Unique Capabilities
Even beyond this framework, bioelectronic medicine may introduce revolutionary new capabilities.
One tantalizing possibility is using bioelectronic medicine as a diagnostic tool. Previous research has suggested that the body produces a unique response to each infectious agent over time. Thus, these “time-series” patterns can accurately predict the disease-causing agent and could be used to guide effective treatment.
“The goal is to build a pathogen library,” Lerman said, “where we would be able to identify the signature of each pathogen and then try to intervene with the correct amount of neuromodulation to impede the inflammation associated with that infection and to make that infection less severe.”
Disease signatures have been shown in waveform data (EEG, respirogram, temperature), but Lerman and colleagues suggest that monitoring the activity of the vagus and other nerves in the autonomic (involuntary) nervous system could provide key information for this effort.
Another area where bioelectronic medicine could have an oversized impact is mental health. Recent research has highlighted inflammation and the immune system as key players in a host of mental health conditions.
“Mental health disorders — including post-traumatic stress disorder, major depression disorder and general anxiety disorder — are all at the core very much related to the ‘neuro-immune axis’ and regulation of inflammation,” Lerman said. “Further pathological processes within the vagus nerve are known to occur with certain neuroinflammatory disorders such as long COVID and certain types of Parkinson’s disease.” Many different viruses and/or pathogen constituents can transmit from the gut via the vagus nerve to the brain, or, because of the inflammation in the gut, result in peripheral inflammation that also causes problems in the brain.
Lerman suggests bioelectronic medicine could assess brain inflammation to measure the severity of mental health disorders and be tapped to treat them with the precise dosage needed. Autonomic neurography or ANG is poised to be especially useful in clinical trials; it will objectively stratify mental health severity providing clinical trials with a precision medicine measure that can guide specific treatments.
Projects supported by U.S. Defense Advanced Research Projects Agency, National Institutes of Health, Biological Advanced Research & Development Authority, as well as the Office of Science and Technology Policy and other sources of funding and advocacy have brought bioelectronic medicine to this point, Lerman acknowledges.
“There is still a lot of work ahead of us,” he said, “but these next-generation systems have much potential for new avenues of individualized and adaptive treatment.”