PROVIDENCE – On Tuesday, Feb. 12, students enrolled in the class taught by Dr. Patricia Nolan at the School of Public Health at Brown University will present a hypothetical case study on potential changes to the new strategic three-year plan being developed by the Governor’s Task Force on Overdose Prevention and Intervention.

As part of the exercise, the students are being challenged to expand successful tactics and to rethink tactics that do not appear to be helping the state meet its goals to prevent overdose deaths, using best available data, identifying where support and opposition might come from, and articulating ways to increase chances of success in getting the hypothetical proposals adopted.

One potential non-opioid pain management solution, however, representing an important paradigm shift in treating pain, will probably not be part of the discussion: the use of a non-invasive, hand-held device, known as gammaCore, which through neuromodulation stimulates the vagus nerve for the preventive treatment of cluster headaches and the relief of pain associated with migraines.

Marketed as “power over migraine pain in the palm of your hand,” the bio-electric medical device is manufactured by electroCore, a commercial-stage bio-electronic medicine firm headquartered in Basking Ridge, N.J.

In January, electroCore was awarded a five-year Federal Supply Schedule contract for its non-invasive vagus nerve stimulation therapy, which will make gammaCore available to more than 21 million patients managed within the Department of Veteran Affairs, the Department of Defense, the Bureau of Prisons, Indian Health Services and Public Health Services.

Other applications for the bio-electric medical device, including its potential use to treat rheumatoid arthritis and withdrawal from opioids, are now in clinical studies.

ConvergenceRI recently spoke with Dr. Peter Staats, the chief medical officer of electroCore, to discuss the evolving field of bio-electric medicine, which refers to the stimulation and modulation of the electrical nervous system, in order to modify various diseases in the body.

In the interview, Staats drew the distinction between previous uses of neuromodulation, which he described as an end-of-the-road therapy, involving implantation of devices, to a change in the algorithm, envisioning neuromodulation as a beginning-of-the-road therapy.

Because the gammaCore device is non-invasive, Staats explained, “It really does increase the applicability to many, many more people.”

From a business model perspective, Staats continued, “As opposed to trying to sell a device that would otherwise cost $40,000 being implanted in somebody, and then you have to recoup the cost of $40,000, we are offering the device at a really nominal cost, just like a branded drug would be, and people only pay for it if they are actually getting good relief.”

By not making it expensive, by making it non-invasive, by making it quite a bit safer than a lot of other approaches, by [advancing] the field of neuromodulation and bio-electric medicine, Staats said. “We are really coming up with a whole new field of caring. And, I hope, changing the algorithm about how we think about treating patients with pain, as well as other systemic and inflammatory diseases.

Here is the ConvergenceRI interview with Dr. Peter Staats:

ConvergenceRI: Your work seems to be opening up an entirely new window, or door, into how people are treated for pain. Is that accurate?
STAATS: Sure. One of the things that is really interesting about [what] we are doing is the confluence of a variety of different advances in various fields that are coming together.

First of all, there is the evolving field of bio-electric medicine, which refers to the stimulation and modulation of the electrical nervous system to modify various diseases in the body. It is an offshoot of the field of neuromodulation that’s been around for a long time.

But the [application] of bio-electric medicine in modifying disease, from rheumatoid arthritis to headache disorders, using electricity to do that, is kind of new and novel.

The second thing that is kind of new and novel is that we are taking the use of neuromodulation, or stimulation of an electric field, non-invasively. What does that mean?

We are taking neuromodulation from an end-of-the-road therapy [through implanted devices], from an option that was only feasible for a very select few, and increasing its applicability to many, many more people.

ConvergenceRI: What has been the uptake of the gammaCore device to treat migraines, the hand-held device that is now on the market. I read a news release on your website that said that the Veterans Administration had given a large endorsement, if that is the right phrase, of the product. Is that accurate?
STAATS: In the military system, there is something that is called the Federal Supply Schedule. And, once a device has been demonstrated to be effective, by FDA standards and by Level 1 studies that we’ve done, [our] product was accepted as part of the Federal Supply Schedule, which covers the Veterans Administration and the Department of Defense and Indian Health Services, [among others].

That makes it really quite simple for neurologists to start to utilize this device for patients with migraines and cluster headaches.

It is an important milestone for us [to reach], I think, to be able to treat active military personnel with headaches [through the use of our device] – without having to use drugs or narcotics.

There is a tremendous problem with opioid addiction in America. Last year, I believe there were something like 70,000 deaths in some way related to opioids.

Certainly, not all of those are related to a condition that we are prescribing [our device] for. But it is wonderful to have a therapy like this that is safe, and effective, and really an alternative to opioids in the world today.

ConvergenceRI: In addition to treatment for migraines and cluster headaches, your company is also beginning to explore potential treatments for conditions such as rheumatoid arthritis, where it seems there would be a great potential upside for your product. Have you received any pushback from potential competitors in Big Pharma, such as Amgen?
STAATS: At the end of the day, what we’re trying to do is to improve patient care. I worry less about what Amgen thinks and focus more on what we are doing for patients: what would you want your mother or daughter to get? How would you like them to be treated?

We have more than 20 years of really good science on this kind of anti-inflammatory pathway. It has been demonstrated, time and time again, that if you stimulate the vagus nerve, you can modulate inflammation throughout various areas of the body, most notably in the spleen. One can modify the production of various interleukins that are associated with various inflammatory disorders.

The basic science on this has been tremendous. And we’re just now really getting started on our rheumatoid arthritis trials here in the U.S. to demonstrate efficacy without [implant] therapy. We’ve done all the [research] work to demonstrate that we can stimulate the vagus nerve very similarly to an implant. We’ve demonstrated the effect on the vagus nerve in a dozen different ways. There is no question that [our non-invasive device] does a lot of the same things that the implants do,

Now that we can do this without having to do surgery, I suspect that we will be able to do these studies much more quickly.

ConvergenceRI: Getting back to the use of opioids, beyond the treatment for headaches and migraines, are there other applications through which the stimulation of the vagus nerve would work in terms of a reduction of perceived pain?
STAATS: So, there are a variety of different mechanisms by which the vagus nerve stimulation works in modifying the pain pathways in a variety of headache disorders, most notably in migraines and in cluster headaches.

And, one of the areas that has been demonstrated is with glutamate, which is an excitatory neurotransmitter, which is up-regulated in various models of migraines.

There are also studies demonstrating modulation of norepinephrine and serotonin; there are studies looking a cortical spreading depression, which is the electrical activity of the brain that is hyperactive in patients with migraines.

Vagus nerve stimulation has been demonstrated in these various models to decrease the hyper-excitability back to a much more normal state.

This is a kind of long-winded answer to say, yes, these diseases hurt, and in fact, 69 percent of patients going to a community-based emergency room with a complaint of migraines, are offered an opioid.

That’s not the case at the higher end academic programs, but in the community, that’s what is done.

And it is really important, don’t you think, to have something that is an alternative to the opioids that is highly effective and safe to help some of the pain problems.

We are not making any claims that this [device] can help solve addiction.

But what causes addiction? It is [often] repeated exposure to opioids. We hope that if this [device] is appropriately used, we are going to have less use of opioids. So, we think, by corollary, there would be less of problem out there for people eventually to get hooked on medications.

I’m not one to say that opioids are all bad. That’s not really my position. But, if there are alternatives, we should be thinking about them.

ConvergenceRI: In Rhode Island, at the University of Rhode Island, there is pioneering work being done by MindImmune, a drug development research firm embedded at URI, working on different approaches to Alzheimer’s and Parkinson’s diseases, looking at inflammation and the brain’s own immune system.

Are there potential collaborations with your work on vagus nerve stimulation and how that affects inflammation, and how the brain’s immune system responds, to inflammation?

I hope that I asked that question accurately, given my non-scientific background.
STAATS: You really nailed it. Most people, when I talk about our work, don’t get the immune reaction [involved], because it is kind of cutting edge. But I think that some degenerative diseases of the brain will turn out to have inflammation of the central nervous system as part of their disorder.

Vagus nerve stimulation has been demonstrated in animal models to modulate inflammation. We have yet to demonstrate in clinical trials anything with Alzheimer’s or Parkinson’s diseases, but it certainly makes sense, from a scientific standpoint, that it could be an area that we could look at in the future.

ConvergenceRI: How precise are the calculations involved in measuring the effects caused by vagus nerve stimulation? Have you had to create your own mathematical modeling?
STAATS: We have been looking at the various densities of the tissue and what an electric field does, in terms of fat content and water content. We are not stimulating the vagus nerve in a specific manner; we’re activating everything. Some people will say: I need to find the exact pathway.

But, the truth is, the effects are positive, so we may not need to find this exact frequency that goes to one area or another.

ConvergenceRI: You don’t expect anybody to show up at your door and ask: “What’s the frequency, Kenneth?” [In the 1980s, a stranger asked that question of Dan Rather at the entrance to his apartment in New York City, and when Rather couldn’t answer, roughed him up, which led to the REM song, “What’s the frequency, Kenneth?”]
STAATS: [puzzled]

ConvergenceRI: It’s a joke.
STAATS: [laughing] No, I don’t. But it does happen that I do get those questions all the time.

ConvergenceRI: Your firm has completed an IPO.
STAATS: The IPO was quite successful. We are not in the process of building out our sales team, spending time with the VA and DOD systems right now. We are also having continued conversations with insurance companies.

Rather than just talking about how safe we are and how effective we are, we are also having conversations around costs. In some populations, when they use our therapy and make it part of their routine care, we may actually save money for the system.

It is kind of an interesting development: as a new drug or new device therapy, we are not adding costs, we may actually be subtracting costs for some patients who need our therapies.

ConvergenceRI: Are you exploring testing your non-invasive bio-medical neuromodulation device as a potential therapy for those who are experiencing withdrawal from addiction?
STAATS: We have started a study, for which I do not have any of the data back yet, on patients with addiction disorders. Actually, we’re not doing the study, we are partnering with somebody who is doing the study at a major academic university, looking to assess whether or not the therapy works with helping [ease] withdrawal symptoms with addiction.

ConvergenceRI: Are there things I haven’ asked, that I should have asked, or things that you would like to talk about?
STAATS: I think we had a nice discussion overall. Neuromodulation is a really rapidly expanding area, with all kinds of innovations being developed. We are the tip of the spear in terms of bio-electric medicine, making it available to a broad swath of patients.

Pharmaceutical companies are beginning to get interested in this. Typically, they are not so interested in medical devices. But when they see [that our bio-electric medical device] works like a drug, acts like a drug, and distributes like a drug, they will become more interested in the therapy.

I think, eventually, a pharmaceutical company is going to want to become very involved in this.