Brain Storm

Can the brave new world of neurotechnology help an OHSU surgeon find a cure for obesity?

 

In 1990 Oregon Health & Science University neuro-surgeon Kim Burchiel performed the very first Deep Brain Stimulation surgery in North America, as part of a Food and Drug Administration-approved clinical trial for patients suffering from the debilitating symptoms of Parkinson’s disease.

Slowly, carefully, he placed tiny electrodes deep in the brain of his patient, an airline pilot with an aggressive case of Parkinson’s. Later, the electrodes were connected by an ultra-thin wire to a small battery pack, delivering impossibly small doses of electricity to the part of the brain that regulates the tremors and stiffness that characterize the neurodegenerative brain disease.

The response was dramatic — immediately, his tremors all but disappeared. “I’ll never forget him,” Burchiel says. “He was willing to try something entirely new, something that had never been done before. I’m forever grateful to him.”

In 2015 Deep Brain Stimulation, or DBS, is still a highly effective surgical treatment for the tremors associated with advanced stages of Parkinson’s disease and other movement disorders, like essential tremor and dystonia. With more than 100,000 successful surgeries performed nationwide, DBS is considered one of the most consistently safe and effective treatments for any medical condition, of any kind.

Now, three decades after bringing DBS to the U.S., Burchiel, 65, has placed himself on the precipice of what could be another groundbreaking leap forward for his field. He aims to make a smaller, faster and smarter DBS device. The new contraption is also designed to be applied to one of health care’s most daunting and expensive issues, and one that seemingly has no relation to neurogenerative disorders — obesity.

With the Knight Cancer Challenge and media darlings like OHSU’s cancer researcher Brian Druker dominating regional headlines, it’s easy to miss lower-profile, slower-moving programs and projects like neurosurgery and DBS research. But if Burchiel, who last year launched CereMod, a startup aimed at commercializing DBS innovations, is the tortoise to the Knight Cancer Institute hare, the idiosyncrasies of his research are equally illustrative of larger trends — in this case, the rise of modern-day brain science, a potent mix of neurology, smart technology and electronic medicine.

In 1990 Burchiel couldn’t have imagined that all roads, including obesity, led to the brain. But as researchers around the world continue to push forward, slowly unlocking the secrets about where, why, and how specific problems in the brain work — and how they can be treated — a new era of opportunity is opening up. “This is an extraordinary time for our field,” Burchiel says.

A 2012 study 
from Cornell 
University estimates 
that annual obesity-related 
health care costs are near 
$200 billion, about

21% of total U.S. health care costs.

By 2030 projections estimate
an additional $43 billion
to $66 billion per year will be
added to the tab.

Back in 1988, when Burchiel joined a then-modestly sized neurosurgery division in OHSU’s general surgery department, things weren’t quite so extraordinary. “I’m proud of what this place has become, out of something that, in the ’80s, frankly didn’t look that promising,” he says. The research environment improved dramatically in the late 1990s, when the program expanded from a smaller division of general surgery to a department of its own, now carrying a national reputation in a variety of sub-specialties, and growing institutional support.

Just this year, OHSU chose Deep Brain Stimulation as its pilot program for national expansion. Modeled after programs at other major hospitals, patients from all over the country will visit OHSU — and, for now, Burchiel — for the surgery.

That growth trajectory mirrors national trends. Although the promise of “unlocking the brain’s potential” has been around for a long time, technological advances and public funding and enthusiasm around neurology are at an all-time high. In the 1990s, mapping the human genome was all the rage. Today the race is on not just to map the inner workings of the mind but to develop the treatments and technologies to alter them.

DBS is part of the moment. In 2013 the federal Defense Advanced Research Projects Agency, known as DARPA, launched a $70 million initiative to jump-start the next generation of Deep Brain Stimulation technologies, as part of the larger Brain Research Through Advancing Innovative Neurotechnologies, or BRAIN, initiative. Announced by President Obama in 2013, the program channels federal and nonprofit foundation funding toward mapping the human brain. Across the pond, the European Union’s $1 billion investment in the Human Brain Project at the Swiss Federal Institute of Technology has a similar goal.

“Your brain is who you are,” says Christof Koch, president and chief scientific officer of the Allen Institute for Brain Science in Seattle. In 2012 the Institute launched a highly publicized research campaign to address fundamental questions about brain function, aiming to grow the knowledge fund available to the global research community.

“The fact that you know who you are, and remember what you had for breakfast, and remember your first kiss — that’s not the heart, although we like to think that on Valentine’s Day,” says Koch. “It’s the brain. It’s the brain that we need to understand if we want to understand our own minds, when it’s normal, and when it’s sick, with depression, paranoia, autism or Parkinson’s.”

No one knows that better than Burchiel. Neurosurgeons work in a subset of a subset of an already specialized field of medicine — and it’s this relatively tiny group that has insider access to the command center of the human body. “We’re the only people on the planet with regular access to the brain,” he says. “That means we can, and have done, all kinds of research that has helped us unravel this mystery.”

More than two decades after taking his post at OHSU, Burchiel’s growing neurosurgery department was joined by the Neurological Surgery Research Lab, bringing researchers Chris Madden and Sean Morrison with it. Where their research on metabolism met Burchiel’s decades of clinical and surgical expertise, CereMod — “modulating the cerebellum” — was born.

This new venture is just the latest in a long and steadily progressive career for Burchiel, born in high school-age aspirations to join the medical field and — more than 50 years later — showing no signs of flagging. “I’ve always believed you’ve got to stick to your task,” he says, speaking from his corner office on the eighth floor of OHSU’s Center for Health and Healing in the burgeoning Southwest Waterfront district, a sleek new symbol of change and a far cry from his early offices up the hill.

Burchiel’s stick-to-itiveness borders on the epic: first, the campaign to bring DBS to the U.S., followed by years of clinical trials and a successful push to secure widespread insurance coverage for the therapy. Along the way, he served terms as president of the Society of University Neurosurgeons and the Society of Neurological Surgeons, and he literally wrote the book — a few of them, actually — on surgical methods for the therapy, pushing forward advancements that changed the way it was performed.

Despite these successes, the state of the basic DBS technology has remained static. The electrodes are smaller, as are the battery packs that power them, which carry a longer charge. But just miles away from the unstoppable march of progress carried by Moore’s Law and tech giants like Intel, 25 years seems like a long time to wait for better batteries. For now, only one DBS device is available in the U.S., and for all of its success when used for Parkinson’s and tremor, the applications for the therapy are relatively few.

“DBS technology hasn’t kept pace with technological advances in general, microelectronics and implantable devices in particular,” Burchiel says. He speaks slowly and methodically, the manner of a man well versed in translating the very complicated for the uninitiated. “In the time I have left, I hope to be able to push that forward.”  His solution? To deliver a one-two punch to the stagnant DBS device, and applications for it, on today’s market.

Chronic obesity isn’t a neurological disorder like Parkinson’s or Alzheimer’s, which have responded well to DBS treatment since its earliest days. Nevertheless, Burchiel posits that the most severe and intractable cases of obesity, those that fail all other treatments, are due to faulty hardwiring in the brain. Researchers around the world are hard at work mapping the areas of the brain that control autonomic and voluntary bodily functions, and decoding the not-quite-infinite number of electric signals that our brain and nervous system traffic in.

“If DBS is going to take a leap from the ’60s to the 21st century,” Burchiel says, “we’ve got to understand the traffic better.”

Burchiel thinks he’s found a way to do this for the unique maladaptation that leads to chronic morbid obesity. In other words, he thinks he’s found the exact spot where the brain regulates metabolism, a notoriously tricky area to find and treat.

“It’s a very challenging area in the brain to get to,” says Ali Rezai, a neurosurgeon at Ohio State University who is working on a late-stage clinical trial for another application for DBS, also for obesity. “If Burchiel has come up with a new target in the brain, that’s fantastic.” Burchiel is a well-respected figure, adds Rezai. “He knows his stuff.”

In the cutthroat world of medical research, Burchiel holds key details of how the device will work close to the vest. He estimates CereMod has another eight years between here and the marketplace, leaving ample time for a competitor to jump in the game. “I can’t tell you exactly where [the spot] is,” he says.

The brain regulates metabolism, and DBS regulates the brain. It follows, then, that DBS could regulate metabolism. Brain surgery still seems extreme though, right? Wrong, says CereMod “co-inventor” Chris Madden, who is leading the startup’s research  — so far, successful —  in lab rats. “That [misconception] comes from not understanding the advanced state of clinical neurosurgery,” Madden says. “When Burchiel implants a stimulator in someone with Parkinson’s, it takes a couple of hours and they stay here one night. They’re out the next day.”

A new application for DBS, now only used for a small range of medical issues, is part of the CereMod project. So is bringing the device into the era of “smart” machines. In short: Burchiel wants to push the DBS device forward from glorified pacemaker technology to a sensing device that works on a “closed loop,” monitoring and regulating electrical activity at the implantation site moment by moment.

{pullquote}DBS technology hasn't kept pace with technological advances in general, microelectronics and implantable devices in particular.     {/pullquote}

Consider the pacemaker: In its first iterations, it was a simple impulse generator, geared to deliver the same amount of electricity all the time. Later updates allowed it to “listen” to the heart, waiting for a drop in heart rate to deliver an extra jolt of electricity. This still isn’t truly responsive — that is, it doesn’t regulate the electrical activity of the heart all the time. Instead it waits for something to change or go wrong before leaping into action.

DBS hasn’t even gotten this far yet. Today’s devices deliver an electrical output, but they don’t read, understand or respond to any of the signals that the brain and central nervous system send and receive. The strength of the electrical output has to be manually tuned and can’t be changed in between appointments. “It’s ‘set it and forget it’ technology,” Burchiel says.

It stands to reason that the smartest part of the human body deserves a smart device — but until now, that hasn’t been the case. 

Why the slow speed of progress for DBS, when just down the road from OHSU, Intel seems to be shrinking microprocessors by miles a minute? First, scientists still don’t understand exactly how the device works. They can measure the effect — that is, they apply electricity and the tremors go away — but exactly why it happens is still something of a mystery. 

The demand for innovation has also been low: Only one approved DBS device, by global medical device manufacturer Medtronic, is currently available in the U.S. (This is what Burchiel uses in his dozens of surgeries a year.) 

Now, finally, several new devices — some already used in Europe — are poised to enter the market, upping the competition and, through the research and design required for each, providing futuredevice innovators with much-needed information to build on their work.

Researchers see the kind of closed-loop technology Burchiel is aiming for as an integral part of the next generation of neurostimulation therapies — the field that includes things like DBS, spinal cord stimulation for pain management, and a growing number of electrical stimulation therapies in the brain and central nervous system.

Closed-loop technology is especially important for the complex issues at play in neurodegenerative diseases like Parkinson’s and Alzheimer’s, which don’t progress at a predictable rate, or act in the same way from person to person. A device that could listen and adapt to brain activity would be a huge boon to patients with these kinds of conditions, and could carry with it potential for future therapies we can’t begin to imagine yet.

“It’s been a bit of a holy grail for the field,” Burchiel says as he steeples his long fingers. In the silence of his corner office, you can almost hear the gears whirring and turning before he speaks. “We’ll see if it works.”

Researcher Chris Madden (left ) and Kim Burchiel

If Burchiel has figured out how to develop a smart DBS device for use in the brain for any application, including obesity, it would be a groundbreaking discovery. And if CereMod works for obesity, it might work for other conditions, too. “Right now, we’re only looking at this one application for the technology, because we think we’ve figured out how to do it effectively,” Burchiel says. “But that’s not our only goal.”

Cracking the brain’s virtually limitless codes “is the moon shot for this field,” he adds. “There’s not going to be just one major discovery here — this is where the real breakthroughs are going to occur.”


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