Implanted medical devices can be used to treat a number of medical conditions, including regulating heart function or delivering electrical stimulation to targeted areas of the brain to treat essential tremors caused by Parkinson’s disease. A new implantable device, to be designed and developed by scientists at the University of Minnesota Medical School, may be able to help treat common but serious mental illnesses like depression and PTSD.
A team of researchers, led by Alik Widge, M.D., Ph.D., assistant professor in the University’s Department of Psychiatry and Behavioral Sciences, has been awarded a $6.6 million grant from the National Institute of Mental Health (NIMH) to develop the device, which would use electrical impulses to help misfiring brain rhythms fall into synchrony.
In a departure from the pace of typical academic research, this team — which includes Widge; Greg Molnar, Ph.D., a medical device expert and associate professor in the University’s Department of Neurosurgery; and Mahsa Shoaran, Ph.D., of the Swiss Federal Institute of Technology in Lausanne, Switzerland — has put the implant project on the fast track. They hope to have a device that is ready for first in-human use in as little as six years.
The size of the grant points to the project’s promise, Widge said: “The National Institute of Mental Health doesn’t normally give out this kind of money. $6.6 million is a large grant for still a relatively junior professor.”
The grant, Widge said, is a vote of confidence for his team, which includes “clinicians who understand the problem and an expert with deep background making and bringing to market next-gen medical devices.” And, he added, the fact that the medical school is located in the Twin Cities gives his project an edge: “We are the Silicon Valley of implantable medical devices.”
Molnar has a deep background working in the implantable device industry. He was employed for more than a decade at the medical technology giant Medtronic, helping to refine and develop the multinational’s implantable-device line.
When Widge approached him with his idea, Molnar was immediately enthusiastic about its prospects.
“It’s a big deal,” he said. “It is the first grant I’ve seen at the University that is truly focused on translation.” This is not pie-in-the-sky long-horizon academic research, Molnar added. The end result of this project will be a device that has the potential to change the way mental illness is treated. “The deliverable is going to be a working first-in-human-ready closed-loop deep-brain stimulation system. That’s impressive.”
‘A new mechanism’
The technology for treating brain disease with implantable devices already exists: For many years, for instance, people with Parkinson’s disease have been treating the debilitating tremors and other symptoms associated with the disease with a device called a neurostimulator that delivers electrical stimulation to areas of the nervous system that control movement, blocking abnormal electrical signals.
A Parkinson’s neurostimulator works much like a heart pacemaker. Widge explained that his device, while it will be able to use much of the hardware designed for other implantable devices, will require specific custom electronics to work on a different, more targeted level.
“This is a new mechanism of action different from anything on the market,” he said. “This is something that is designed to get at the biology of mental illness in a way that wasn’t possible before.”
Widge and his colleagues see mental illness largely as a physical disease of the brain that can be treated by altering the way different parts of the brain communicate with each other.
“Most mental illness — addiction, PTSD, depression, anxiety, OCD — all of these conditions in different ways are caused by breakdowns — or in some cases too much communication — between certain parts of the brain in certain sub-networks,” he said. His team’s device will use targeted electrical stimulation to help build healthy connections between different areas of the brain.
Widge likes to use computer metaphors to explain his device. “If you have a program on your computer or phone that goes a little bit rogue, it can’t let go of whatever resource it is using,” he said. “You get that spinning beach ball and the whole system blocks up. If you can just fix that one thing that’s causing the problem, if we can close that one small program and make a little tweak, the whole system can get back into alignment and function better.”
By taking this direct, physical approach, Widge’s device has the potential to upend the way mental illness is treated.
“When we think about what we use right now to treat mental illness — primarily medication and talk therapy — they don’t do what we’re talking about,” he said. “They don’t physically intervene. But this device will. Most experts agree that we need circuit-directed therapies if we want to get a handle on this illness and achieve the gains that have yet to be achieved.”
The U of M’s proposed device will use existing implantable device technology, but will require unique custom electronics to deliver targeted electrical impulses to the brain, Widge said.
“Deep-brain stimulation hardware that was developed to treat Parkinson’s disease can’t do what we need it to do. It wasn’t designed for that. It was built off a rewired cardiac pacemaker. We have the stimulation hardware, but we don’t have the right signal processing yet.”
His team will be involved in developing custom circuitry to precisely time stimulation relative to ongoing brain activity.
“If the brain rhythms are in synch, one area is getting ready to fire as the volume of information comes in from the first,” Widge explained, switching mid-stream to a sports metaphor. “Think about the receiver or outfielder who knows when the ball is going to be coming to him and is standing there ready to catch it. The catch is effortless and they are right there where they need to be. That’s what brain synchrony does.”
Fast track possible ‘only in Minnesota’
While Widge is confident that mental illness can be treated with implantable electrical stimulation, he credits Molnar with helping him understand that his project could be developed and delivered in record time.
Widge had been working in an animal lab for years, experimenting with stimulation patterns that can achieve the kind of communication between brain networks that is needed for his device. One day, he was talking to Molnar, explaining that he knows his device can work in rats but he didn’t know how to take the next step of getting it to work in humans.
Molnar, with his deep background working in the implantable device industry and consulting with Minnesota companies specializing in developing the technology, was enthusiastic about Widge’s idea. He told Widge, who’d been lured to the U of M from Harvard and MIT, that Minnesota was the perfect place to see his project through to completion.
“Greg said, ‘We have four contract medical device manufacturers in the Twin Cities alone,’” Widge recalled. “He explained that in our ecosystem in this state, what we’ve got is a set of companies that have the individual parts of an implantable neurostimulator on their shelves ready to mix and match. This is where the ‘Only in Minnesota’ story comes in.”
Once Widge and his colleagues develop the custom electronics needed for their device, Molnar explained, they’ll have their pick of medical device manufacturers primed to take the next step.
“All these companies do is wait for someone to come up to them and say, ‘I have a new medical device idea. I need a prototype made,’” Widge said. “Once we build that one chip that runs the device, the rest is all available off the shelf. We just need to pick the right manufacturing partner to integrate our innovation with what they know how to do up to FDA standards.”
Support from the University of Minnesota’s MnDRIVE initiative aimed at boosting academic research and development in the state’s medical technology industry also gives Widge and Molnar hope that their device can be developed and tested in a relatively short period of time.
That kind of support, Widge said, “is why I moved here. I was at Harvard and MIT before I came here, but they could not do what we can do here in Minnesota. This would not have happened if I had stayed in Boston.”
That kind of overwhelming support for research, Molnar added, will help the team move their research to practical application in record time.
“This isn’t your classic, ‘Let’s do this for five years, more research is needed,’ academic project,” he said. “This is taking discovery and literally, with my expertise, putting it into hardware.”
At Medtronic, Molnar said, “We dealt in reality. We wanted to make a product. With this project, the opportunity for collaboration with academia and industry is going to make this grant real.”
Widge said that having Molnar on his team makes him feel that an accelerated timeline for his device’s development is achievable. “At the end of this grant I think we’ll be ready for the animal test that will make it ready for the first in-human in five years. That’s warp speed for the medical device industry.”
Widge’s “optimistic clinician” hat tells him that odds are the first version of the device the team builds will work. But that process will take a few years. “You have to first test it in a pig or a sheep, but then it would be ready for human use,” he said. “My pessimistic research-engineer hat says, ‘Nothing you build will work the first time. You will need to re-build several versions.’”
That said, Widge remains optimistic that this device could be ready for human use in record time. “I’m assuming that in six or seven years we will be doing pilot human clinical trials. This is something that’s needed by so many people, so I am thrilled to think that it could become a reality in a relatively short time.”
A new approach to therapy for people struggling with mental illness is a “big, unmet need,” Molnar said, and because of this he sees many possible uses for the device going forward.
In the future, he explained, “This device will be used for treating depression and all the spectrum of symptoms of mental illness. This will have a huge impact on the quality of life for millions of people.”
One group of people who could benefit from his device are those suffering from PTSD, Widge said. “In people with PTSD,” he explained, “there is a part of the brain called the amygdala that is involved with fear and emotion. The prefrontal cortex provides the context. In PTSD, signals from the prefrontal cortex don’t get through to the amygdala regardless of context. What we can do with this device is restore that communication, get those two reactions to work together and do what they’re supposed to do.”
While the device will help put brain communication back into synch for people suffering from a range of mental illnesses, it will not be a one-and-done therapy. People with the device will still likely need to work with a psychotherapist to understand how best to respond to stress or life change, Widge said: “Our system will have to combine with certain forms of talk therapy.”
And just like any other implantable device, ongoing care is needed to help patients heal.
“This is no different than any other implantable device,” Widge said. “If you get a knee replacement you will get 3-6 months of physical therapy to help you learn how to walk and strengthen those muscles. It’s the same with our device.”