Two Penn Medicine researchers selected for prestigious NIH Director's Awards

Picture a future where embedded medical devices not only treat and teach patients, but learn from them. Imagine chronic pain being managed without the negative side effects of opioids. Penn Medicine researchers are working to make those scenarios a reality. These initiatives are among innovative new National Institutes of Health (NIH) funded efforts that are mapping the future of medicine.

The NIH has selected two researchers from the Perelman School of Medicine at the University of Pennsylvania to receive its prestigious Director's Awards, part of the NIH Common Fund's High-Risk, High-Reward Research Program honoring exceptionally creative scientists. Brian Litt, MD, a professor of Neurology, Neurosurgery, and Bioengineering, was honored with a Pioneer Award for $5.6 million, supporting novel neurodevice research. Gregory Corder, PhD, an assistant professor of Psychiatry and Neuroscience, was selected as a New Innovator Award winner, receiving $2.4 million for research investigating the mechanisms of chronic pain.

This NIH initiative, designed to fuel research endeavors that are more opened-ended and have a potentially broader effect on scientific understanding compared to more traditional research, awards these to scientists to support research over a five-year period. The 2020 Penn recipients are among 85 awardees nationally:

Pioneer award - Ghost in the machine: Melding brain, computer and behavior

The Pioneer Award challenges investigators to pursue new research directions and develop groundbreaking, high-impact approaches to a broad area of biomedical or behavioral science. This award supports Litt's work to develop a new generation of autonomous neurodevices--implanted machines that can question, record, and combine learning algorithms based on neurological signals and feedback to act and alter human behavior on the fly.

In epilepsy, for example, these devices would predict and prevent seizures; in Parkinson's patients, implants will measure and communicate with patients to improve mobility, reduce tremor and enhance responsiveness. Other implants might improve hearing or psychiatric symptoms by querying patient perceptions, feelings, and altering stimulation patterns algorithmically to improve them. The loop is closed in real time, so the host can change their behavior based upon device feedback to improve their health.

Imagine this: A 30 year-old veteran walks into a bar. None of the patrons are aware of the anti-seizure device in his brain, or the traumatic brain injury that requires it. After he drinks a beer, his phone vibrates with a text from the implantable device asking what he's doing and sharing his probability of a seizure has increased. And with a quick explanation from the veteran, the device stimulates and suggests avoiding a second beverage. We're working towards this future, with the help of the Pioneer Award."

Brian Litt, MD, Professor of Neurology, Neurosurgery, and Bioengineering

This is a paradigm shift from today's simple devices, which rely on physicians to give device feedback to patients and change simple parameters by hand during occasional office visits. Litt's goal is to build a foundation for responsive implants that can collaborate with hosts, linking human experience and perception to machine algorithms, actions, and therapy, predicting and preventing events before they start. Not only will the patient teach the device, but the device will teach the patient.

Grant ID: DP1 NS122038-01.

New innovator award - Harnessing cortical neuromodulation to disrupt pain perception

The New Innovator Award supports unusually innovative research from early career investigators who have not yet received a research project grant or equivalent NIH grant. The award will support Corder's efforts to research the mechanisms of chronic pain--a major health crisis in the United States, affecting millions, and a driver of the opioid epidemic.

Corder's goal is to identify which parts of the brain are important for pain perception and which circuits impact pain relief from opioids. He hopes to decode how this neural activity evolves during chronic pain. Once the brain circuits and pathways that contribute to the suffering and perception of pain are identified, they can be targeted for potential therapeutics which could be more effective at reducing pain and without the addictive elements of prescription opioids.

Corder envisions these next generation pain therapeutics leveraging viral-delivered cell-specific gene therapies to disrupt the pain-processing circuits in the cortex. This would will allow patients to sense pain but without the unpleasant aversion.

"We currently have a limited understanding of the neural pathways in the brain that contribute to pain, which has been a significant barrier for treating pain efficiently, without negative side effects. But, if we can identify and understand these circuits, we can then try to rewrite the neural code of pain," Corder said. "Picture being able to specifically target the one desired brain region or circuit that processes pain in order to provide pain relief. This research will help us lay the groundwork for new classes of therapeutics, which could have a profound and broad impact for treating patients with chronic pain, while reducing the burden of the national opioid crisis."

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