An illustration of Bubrick’s project, drawn live during HUBWeek’s live pitch session by Collective Next.

Ellen J. Bubrick, MD, of the Department of Neurology, was selected by a public vote as the winner of the 6^th annual BRIght Futures Prize, a $100,000 award, for her project, “Break the Shake: Ultrasound Treatment for Epilepsy.” The BRIght Futures Prizes support investigators across the Brigham Research Institute (BRI) as they work to answer provocative questions or solve grand problems.

Ellen J. Bubrick, MD, of the Department of Neurology, was first drawn to neurology by the complexity of the nervous system and its disorders. Bubrick was fascinated not only by these disorders, but how patients experience their disease in society. She was particularly struck by the stigma surrounding epilepsy. When she started to see patients with uncontrolled epilepsy, patients who weren’t responding to any medications and seizing a lot, Bubrick decided to specialize in this disease. “I love working at Brigham and Women’s Hospital because this is where the most complex patients come for help,” said Bubrick, “I want to make their lives a little easier and give them better options – it’s what drives my work in the clinic and my research.”

A New Age for Epilepsy Treatment

While most epilepsy patients do respond to medication and can become seizure free as a result, a surprisingly large fraction of patients do not. Almost 20 new drugs have been developed to treat epilepsy since 1993, but none of them have changed this frightening statistic: one third of the patient population remains drug resistant. This equates to almost a million people in this country alone who do not respond to medications, and for many of these patients, epilepsy surgery is not an option. As the director of the Epilepsy Surgery Program at BWH, Bubrick sees many patients from this drug resistant group, many of whom are not eligible for epilepsy surgery, for a variety of reasons. “I started to feel like I had to do something for this group,” Bubrick explained.

In spring 2017, G. Rees Cosgrove, MD, a physician in the Department of Neurosurgery, suggested that Bubrick connect with members of the Focused Ultrasound Lab at BWH, led by Nathan McDannold, PhD, to discuss the possibility of using high-intensity ultrasound as a new surgical treatment. Bubrick met with Spencer Brinker, PhD, a postdoctoral fellow in the Focused Ultrasound Lab and they began discussing this new surgical technique for epilepsy treatment. During their conversation, Bubrick explained to Brinker that a new surgical treatment was not what epilepsy patients needed most. “If an epilepsy patient is a candidate for surgery, they have options, we don’t need another surgical option,” said Bubrick. “What we need is something for the drug-resistant non-surgical epilepsy patients.” Together they came up with an idea: what if, instead of using high-intensity ultrasound, they use low-intensity ultrasound to treat the non-surgical patients?

Bubrick and Brinker began sketching out a plan. They envisioned delivering low-intensity focused ultrasound beams using a handheld, custom-built device. The ultrasound beams would focus together at one point, infiltrate the skull and disrupt the tissue in the region of the brain where the patient’s seizures are originating. Low-intensity ultrasound beams are not powerful enough to melt or damage the tissue, but might be strong enough to sufficiently disrupt the tissue and disturb seizure production.

Bubrick was intrigued by the idea and checked to see if there might be evidence in the literature to support it. She found that preclinical trials have shown promise for the technique’s success. When the low-intensity ultrasound beams are focused on tissue in animal models, the EEG recording of brain activity quiets down. Bubrick and her team wanted to see if the technique could have the same effect in epilepsy patients, who have excessive brain activity that causes seizures. But in order to bring their idea from paper into the clinic, they needed financial support. Bubrick had heard about the Brigham Research Institute’s annual BRIght Futures Prize competition and, in the hopes of getting funding to begin a pilot clinical trial of the technique, decided to apply on her team’s behalf.

Stepping Outside her Comfort Zone

Sitting in her office in the Neurology Department on a recent Friday afternoon, Bubrick explained the details of her project with ease and comfort, comfort she says she didn’t have during the voting process for the BRIght Futures award. “I don’t like being in the spotlight,” said Bubrick. As someone who had never been on social media before the campaign, Bubrick truly pushed herself outside of her comfort zone to advocate for her patients and the project. She reflects on how amazing the support was that she received from her patients and the wider epilepsy community, who were grateful to have been given a voice.

“I feel obligated to stand up and say that these patients deserve good treatments and deserve to have studies funded to come up with good treatments,” said Bubrick. She explained that while she is relieved to have won the BRIght Futures award and excited to begin her clinical trial, she is also thankful to have had the opportunity to raise awareness about epilepsy during the campaign.

Looking Ahead

This spring, Bubrick and her team plan to begin a pilot clinical trial with 10 drug-resistant, non-surgical patients. While her interests lie deeply with these patients, Bubrick believes that this device could be beneficial to other neurological disorders, including mood disorders. “We’re at the beginning of neuromodulation,” said Bubrick. “Stimulating tissue seems to make it stop doing the bad things it was doing. I hope that neuromodulation is successful in providing a new treatment option, not just for epilepsy patients, but for patients suffering from a wide variety of neurological disorders.”