Since the time of Paul Ehrlich at the turn of the 20th century, the pharmaceutical industry has been seeking “magic bullets” to treat disease – drugs that interact with a therapeutic target with such specificity and selectivity that side effects are non-existent. Modern medicinal chemistry allows the construction of such drugs, based on assays with highly purified proteins, cells in culture, and other finely detailed approaches. Once drugs are ingested into the body, however, such details are no longer controlled. They circulate throughout the body, where they may interact with and affect entirely unrelated biological processes. They can also be metabolized into other compounds, which can have similar off-target effects. Dr. Ehrlich’s vision of pharmaceutical magic bullets has yet to be realized, but an emerging new field of medical research may re-invigorate his concept.
All major organs of the body are innervated, allowing the brain to both monitor and regulate organ function. Bioelectronic medicine leverages these neural pathways to regulate therapeutic targets and treat disease. nerve-stimulating or nerve-blocking devices, either implanted on a nerve or held against the skin, have the potential to modulate specific nerve activity, elicit a specific change in organ function, and restore health, without the complicated side effects of pharmaceutical agents. Such devices are already in clinical trials to treat inflammatory diseases such as rheumatoid arthritis (RA) and colitis.
Rheumatoid arthritis, a disease of the immune system, is characterized by harmful inflammation in the joints. Pharmaceutical agents developed to date for RA, including monoclonal antibodies (the closest modern medicine has to Dr. Ehrlich’s magic bullets), are plagued by harmful and sometimes lethal side effects. Investigators at the Feinstein Institute discovered in the late 1990’s that electrically stimulating the vagus nerve could turn off the immune system pathways associated with rheumatoid arthritis, colitis, and other inflammatory diseases. This technology has been licensed to a biotechnology company, SetPoint Medical, and clinical trials of their novel bioelectronic medicine device are underway for rheumatoid arthritis and colitis.
Inflammatory diseases are just the first examples of diseases that can be targeted with bioelectronic medicine technologies. Every organ of the body is innervated, and thus it is reasonable to hypothesize that modulating neural signals with bioelectronic medicine devices may be an effective therapy for a large number of diseases – and may even be effective for diseases that do not have a pharmaceutical treatment available. Work currently underway at the Feinstein Institute is seeking bioelectronic medicine treatments for bleeding, paralysis, hypertension, diabetes, and others.
The core competency that allows the Feinstein Institute to succeed in the complicated field of bioelectronic medicine is collaboration. In order to develop therapeutic devices, our investigators need to work in interdisciplinary teams that include molecular and cellular biologists, who identify therapeutic targets; neurophysiologists who map neural pathways and understand how nerve fibers propagate signals; and neurotechnologists, who are typically engineers and physicists who specialize in stimulating, blocking, recording and analyzing nerve signals. Key to this process are the molecular and cellular biologists who identify therapeutic targets – understanding the mechanisms of the diseases the devices will treat brings pharmaceutical-grade scientific rigor to the medical device development process.