By Thomas Lee
ROCHESTER, Minnesota – The pacemaker and implantable cardioverter defibrillator revolutionized heart medicine (and gave birth to a multi-billion dollar global industry) by successfully blending detection and therapy into a single, “smart” device. The technology notices a faulty heart beat and automatically delivers an electric shock to correct it.
Now researchers at the Mayo Clinic are perhaps a year away from commercializing a similar device for deep brain stimulation, a nascent but growing way of using electricity to treat neurological disorders like Parkinson’s disease and depression.
The device, called the Wireless Instantaneous Neurotransmitter Concentration System, can monitor and record electro-chemical reactions in the brain. The technology excites outside experts who hope WINCS will eventually produce a system that independently delivers the proper amount and frequency of electricity to a patient’s brain, based on real-time data.
“This is a potential game changing advance” in deep brain stimulation, said Dr. Robert Levy, a professor of neurological surgery and radiation oncology at Northwestern University’s Feinberg School of Medicine in Chicago. However, it’s “still far from clinical application,” he said.
Although the Food & Drug Administration approved DBS devices in 1998, the technology is only now beginning to take shape. Last year, Medtronic Inc. of Fridley, Minn., whose founder, Earl Baaken helped invent the pacemaker, received FDA approval for its Activa RC and Activa PC DBS devices, designed to treat Parkinson’s, essential tremor, dystonia and obsessive compulsive disorder.
Nevertheless, DBS remains deeply misunderstood by doctors and patients, Levy said. The lack of good clinical data supporting efficacy stems partly from the high regulatory barriers set by the FDA, he noted.
The brain, itself, is also the problem. Perhaps the most complicated and unknown organ in the human body, the brain consists of billions of complex and intricate series of chemical and electrical pathways. So while scientists know DBS can help alleviate the symptoms of Parkinson’s, such as loss of motor control, they don’t know exactly why.
“DBS hasn’t been well defined,” said Dr. Julie Pilitsis, director of the neurological surgery department at UMass Memorial Medical Center in Worcester, Mass. “The mechanisms are not understood. It’s mostly trial and error.”
In other words, doctors have no way of measuring whether DBS works, other than observing its effects on patients. And sometimes, those effects aren’t good.
In a major study published in the Journal of the American Medical Assn. last year, researchers examined 255 patients over a six-month period and compared the results of patients treated with a Medtronic DBS device to those given standard therapies, such as drugs. The study concluded the DBS device significantly improved motor control over medical therapy, but patients had a higher risk of “adverse events,” including surgical site infections and cardiac, psychiatric and nervous system disorders.
Enter the Mayo Clinic. Led by Dr. Kendall Lee, the team of engineers and doctors designed WINCS, a kind of all-in-one system that combines digital telemetry (wireless measurement, recording and transmission of data) with amperometry (a chemical analysis that measures electric currents) and cyclic voltammetry (a electrochemical technique that allows doctors to study variations along an electrode by sweeping back through a region just covered).
WINCS will allow doctors to establish the precise relationship between stimulation and the resulting amounts and types of chemicals the brain releases during DBS, in effect making DBS less of a guessing game, Lee said.
“We are trying to figure out how [DBS] works in the brain,” he said. “We want to use WINCS to improve DBS efficacy by determining, in real-time sub-seconds, how much neurotransmitter should get released. Right now, you just hope it will have some benefits for patients. We’re going to know what we are doing to the brain and control the release.”
For example, in a pair of papers published last year in the Journal of Neurosurgery, Lee and his team described how WINCS measures the release by electricity of glutamate acid in rats, a chemical that oversees learning and memory. They system also monitored the brain’s release of adenosine, a key neurotransmitter that scientists believe can control the tremors associated with Parkinson’s.
Based on the data, doctors believe they’ll be able to design DBS therapies that deliver “X” amount of electricity, to in turn release “X” amount of “X” chemical, leading to “X” therapeutic result.
“These results highlight the potential utility of the WINCS to determine selectively the DBS-mediated release of a wide range of neurotransmitters in real time,” the paper said. “The WINCS may thus provide a powerful new technology for intraoperative neurochemical monitoring that is well suited for use during functional neurosurgery.”
Said Pilitsis of UMass Medical Center: “The stimulation can be fine-tuned. Patients normally have their good days and bad days. This could give them some extra stimulation when they need it. It’s definitely the way of the future.”
Experts caution that Mayo faces a number of obstacles. For one thing, diseases cause unique electro-chemical interactions in the brain. For WINCS-guided DBS to work, researchers will need to predetermine each disease’s “marker” in the brain — no easy task, according to Northwestern’s Levy.
And WINCS will only fulfill its potential if it leads to a smart device that can operate on its own in the body, he added.
“Otherwise, it’s just a research tool,” Levy said.
Lee says the Mayo team is discussing possible partnerships with companies to commercialize the technology, which has so far been funded by Mayo and National Institutes of Health grants. He declined to give a timetable for human clinical trials.
At the very least, though, WINCS can provide scientists with ways to understand and improve DBS therapies and demonstrate that they work to skeptical patients, doctors and regulators, Levy said.
“I think it’s exciting,” Pilitsis added. “It’s a great starting point.”