RESEARCH Q UARTER LY

ISSUE 10: JUNE 2019 Shark Tank Awards Innovator Spotlight Series NextGen Scientist Awards Clinical Trials THERE ARE NO RULES“ HERE – WE’RE TRYING TO ACCOMPLISH SOMETHING – THOMAS A. EDISON”

WELCOME LETTER

With thirty to forty percent of those living with being treatment resistant and living with persistent , something radical needs to be done. We need to find new therapies and new innovations that revolutionize the diagnosis, care and treatment of epilepsy. In the June Research Quarterly, you’ll meet entrepreneurs who participated in our Shark Tank event, our early career awardees representing the next generation of scientists, and parents who started companies to tackle challenges that their families are facing.

The creativity and problem-solving capabilities of our community are amazing. Through the Research and New Therapies programs, we are creating opportunities for our community to put those problem- solving capabilities to work. The Foundation is building a stellar track record in supporting epilepsy solutions getting to market. In the last two years alone, five products that received seed funding by the Foundation have reached the marketplace and received regulatory approval including UNEEG Medical (CE approved 2019), Embrace (FDA approved December 2018), Epidiolex® (FDA approved July 2018), Visualase (FDA approved April 2018) and Zeto (FDA approved April 2018). However, our work is not done. As Thomas Edison, arguably one of the most prolific inventors of the last century, once said, “There are no rules here – we’re trying to accomplish something”.

If you have a unique solution that could transform the epilepsy community, we want to hear from you. Please submit your idea through our Shark Tank Awards or Commercialization grants! If you are early on in your career, consider submitting to the American Epilepsy Society (AES) early career funding program. Please go to epilepsy.com/research to learn more

Kind regards, Brandy Fureman, PhD VP of Research and New Therapies www.epilepsy.com/research

Cover Page: Six of the ambassadors for our Let’s Use Our Brains to END EPILEPSY® initiative represent our key stakeholders — individuals with epilepsy, parents, advocates, doctors, activists, staff, volunteers, and donors. The word in the Brain Line Art illustrates one way they are using their brains to END EPILEPSY. This overarching campaign draws attention to the fact that the brain is the source of epilepsy and the brain is the source of the solutions to END EPILEPSY. Credit to Saber, the Artist+Activist, who drew the original art for the Brain Line. Please visit EndEpilepsy.org and create your Brain Line Art.

2 RESEARCH QUARTERLY | JUNE 2019 SHARK TANK AWARDS #EPILEPSYSOLUTIONS

In 2019, 35 individuals or teams entered the competition from across the United States and 8 countries around the world. From this pool, 5 teams were chosen as finalists. The finalists presented on May 24, 2019, at the 2019 Antiepileptic Drug & Device (AEDD) Trials Conference in Florida.

2019 Shark Tank Competition Winners $75,000 AUDIENCE CHOICE AWARD AND $75,000 JUDGES AWARD Inspired by the TV show Shark Tank, finalists give DETECTING SEIZURES WITH AN a 5-minute pitch to our judges about why the EYE-OPENING SOLUTION Foundation should invest in their idea to solve Rachel Kuperman MD the challenges that people living with epilepsy CEO OF EYSZ, INC. face every day. The audience also gets to vote on their favorite project to fund. Thus far there has Dr. Kuperman’s mission is to give clinicians and been a wide range of novel concepts presented patients the tools they need to improve outcomes ranging from: and quality of life. The Eyzs solution will help provide specific, sensitive means for detecting • therapeutic devices, seizures through eye-tracking, a relief from EEG • alert and self-management systems, monitoring currently needed to detect seizures and • devices that prevent personal injury from seizures, seizure-related events. Dr. Kuperman’s desire to • a public awareness campaign abroad. bring this project was motivated by the families she cared for during her ten years of clinical practice Winner(s) of the competition walk away with at the University of California San Francisco designated funding, ranging from $50,000– (UCSF) Bennioff Children’s Hospital as a pediatric $200,000, to help in the development and . commercialization of a new product, technology, or therapeutic concept that support our epilepsy With this project, Dr. Kuperman plans to develop community. and deploy 100 eye-tracking wearables that will be used in a clinical study at UCSF. The clinical study will refine the wearables’ patented seizure- detection algorithm for absence seizures.

2019 Shark Tank Competition Winners and Finalists

R. Kuperman J. McNannay M. Musser A. Turabi S. Chiang R. Moss H. Daneels B. Vandendriessche

RESEARCH QUARTERLY | JUNE 2019 3 $50,000 JUDGES AWARD seizure diary data to estimate a patient’s current FALLING DOWN THE RABBIT HOLE OF level of seizure risk. This data can be sent to both MEDICATION ADHERENCE the user and their clinicians’ electronic health Jody McNannay record (EHR) system and can be diary agnostic. Co-Founder, Curadite, Inc. • This project will carry out an extension of the and parent of a daughter with epilepsy EpiSAT algorithm. The extension will increase Curadite plans to optimize its innovative medication flexibility to accommodate large scale EHR management platform for the epilepsy community. data. EpiSAT will also be deployed as a clinical The platform incorporates intelligent packaging, decision support tool for beta testing with patient reminders, and a clinician dashboard. SeizureTracker.com. Jody brings her experience as a mother of a child with epilepsy to the project. She has experienced SENSOR DOT: LOGGING SEIZURES AND firsthand the difficulty of managing medication EPILEPSY BIOMARKERS AT HOME adherence and transitioning responsibility for Hans Daneels PhD medicine regimens to her daughter as she grows CEO and Co-Founder, ByteFlies older. Benjamin Vandendriessche PhD The Curadite platform provides timely support Chief Medical Officer, ByteFlies for individuals with epilepsy. It also alerts care teams when loved ones are struggling to take • ByteFlies has developed Sensor Dot, a tiny medication as prescribed. Shark Tank funds will wearable that can continuously monitors be used to develop and customize the platform the cardiovascular, respiratory, nervous, and assisting with medication management. They will musculoskeletal systems. Sensor Dot can record also work closely with their research partner to brain activity (EEG), heart rate, activity and complete the pilot design and recruit the clinicians, motion, respiration, electromyography (recording patients, and care teams needed for the pilot. of the electronic activity of muscle tissues), and electrodermal activity. Shark Tank Finalists • ByteFlies also encourages clinicians and researchers to connect with their developing SEIZE THE WHEEL: IMPROVING PATIENT platform to build novel applications that can CARE THROUGH VR help people with epilepsy. Matthew Musser CEO & Founder, Seize the Wheel Shark Tank Judges Areeba Turabi CTO, Seize the Wheel Thank you to the of Minnesota for supporting this event and to our 2019 Shark • A virtual reality driving simulator, coupled with Tank judges! the diagnostic abilities of an EEG, that allows • Page Pennell MD, Professor of Neurology, physicians to determine the level of consciousness Harvard Medical School, Director of Research, of patients during short epileptic discharges. Division of Epilepsy, Brigham and Women’s • The simulator will help doctors make more Hospital, Boston, MA informed decisions with patients about day- • May Liang, Co-Founder, General Counsel and to-day activities like driving and medication Chief Financial Officer, OpenConcept Systems, Inc. managements. • Terrence O’Brien MD, Professor of Medicine, Department of Neuroscience and Medicine, EPISAT: AN EHR-INTEGRATED CLINICIAN DECISION SUPPORT TOOL FOR DETECTING Monash University, Australia SEIZURE RISK • Tracy Dixon-Salazar PhD, Director of Research Sharon Chiang MD, PhD and Strategy, LGS Foundation Neurology Resident at the University of • Timothy Feyma MD, Gillette Children’s Specialty California, San Francisco and creator of EpiSAT Healthcare Robert Moss Do you have an idea for the next Shark Tank? Co-Founder of Seizure Tracker Submissions will open in the fall of 2019, with the finalists presenting at 2020 Epilepsy • EpiSAT is an algorithm that has been developed Foundation Pipeline Conference in Santa Clara, CA. in collaboration with SeizureTracker.com. It uses www.epilepsy.com/sharktank

4 RESEARCH QUARTERLY | JUNE 2019 UPDATE FROM 2018 SHARK TANK WINNERS

3D MACHINE VISION SYSTEM FOR SURGICAL VIRTUAL REALITY MEDICAL SIMULATION NAVIGATION OF THE HUMAN BRAIN FOR THE MANAGEMENT OF Aaron Bernstein PhD President and CEO, Advanced Scanners Joshua M. Sherman MD Faculty Attending – Division of Emergency Jeff Levine MIM, Advanced Scanners Medicine, Children’s Hospital Los Angeles Open resective brain surgery for epilepsy begins Todd Chang MD, MACM with the surgeon creating an opening in the skull. Assistant Professor of Pediatrics, USC-Keck The surgeons rely on image-guided navigation School of Medicine systems to guide their movements within the brain. These navigation systems rely on previously Drs. Sherman and Chang develop virtual reality scanned images of the patient’s brain. The problem simulations to allow the community to better train is that when you open the skull, the brain changes both medical and non-medical professionals for its shape. Advanced Scanners wants to improve highly stressful emergency epilepsy situations. navigational systems and surgical outcomes Usually trainings are done using mannequins and with a rapid, noninvasive 3D scanning approach. actors, which are expensive and constrained to Working with neurologists and neurosurgeons at when the actors are available. In contrast, a virtual the Dell Children’s Comprehensive Center in Austin, reality (VR) module is portable, standardized, and Texas, Advanced Scanners has been developing still allows for an immersive experience. VR allows an intelligent 3D machine vision system. This for training at any time of day. The doctors had system watches during surgery and tracks the partnered up with Oculus’ VR for Good program exposed brain with sub-millimeter accuracy to and companies AiSolve and Bioflight to design improve results in each of the 3 major steps of a prototype module for status epilepticus in the a typical 2-stage epilepsy surgery. These steps pediatric population. This simulation won Best include providing accurate locations of the grid Virtual Reality Education Project at the 2018 electrodes, mapping the surface of the brain at VR Fest and was written up in USA Today and high resolution during surgery to improve what the Buzzfeed. Using an Occulus Simulator, trainees neurosurgeon sees and updating the brain shape can be assessed on their training readiness and changes during real time. This all contributes to a taught what to do in high-stakes situations like more precise navigation system for the surgeon to treating a child in status epilepticus. rely on. This also should make the brain surgery Since their award, they were able to: procedure safer for the patient. • Establish their own company known as SBC Since their shark tank award last year, they were Medical Simulations able to: • Improve training and assessment tests for • Move out of Aaron’s garage into actual office medical resuscitation during status epilepticus space (through an award with WeWork) • Provide diagnostic testing options for doctors to • Submit patents to the US Patent Trade Office train on evaluating during emergency situations • Hire 2 additional staff members to further their • Add an adult status epilepticus module prototype development • Establish partnerships with Medtronic, Medline and Ansys • Secure 1.5 million in follow on funding • Product to be available by the end of 2020!

RESEARCH QUARTERLY | JUNE 2019 5 INNOVATOR SPOTLIGHT 1 #USEYOURBRAIN

Charles and Cynthia Anderson What is your personal put those skills to use. I bought are the co-founders of HiPass connection to epilepsy? a networked security camera Design LLC, makers of SAMi - In 2006, my son had his first and created software that would The Sleep Activity Monitor for tonic-clonic seizure while we were stream the video to a program Individuals. SAMi is an infrared out of the country. He went on I wrote that could analyze our camera-based motion detection medications right away and we son’s movement in the night. alert system used to detect and thought he was well controlled. Anytime there was abnormal record unusual movements at What we didn’t realize was that movement, the computer would night. Charles is personally he was still having seizures in turn on in our room with an alert connected to epilepsy. We spoke his sleep. We had no idea that and live video so that we could with Charles to learn a little bit someone could have seizures check to see if everything was more about his connection to in their sleep and not be aware ok. Over time, we began to refine epilepsy and what motivates that they were happening. It was the algorithm to try and reduce him to do the work that he does. only when we were on another the false alarms. For example, family trip sharing a hotel room if movement starts at the edge that we witnessed his night-time of the camera and goes to the seizures. center, this was one of us going in to check on our son and wouldn’t How often was he having require an alarm alert. nighttime seizures? When we got home, we rigged How did this turn into SAMi (a up a baby monitor in his room. It commercially available seizure turns out that he was having them activity monitoring camera)? a couple of times a month. My In 2011, I read about the Epilepsy wife was losing sleep listening to Therapy Project’s new “Shark the baby monitor throughout the Tank” competition. I presented night in fear that he would have the concept and my prototype a seizure and that we wouldn’t and won the award. I used the know about it. Sleep, Seizures award money to fund turning and Impact on Families my prototype into the product we have been selling for the last What did you decide to do? seven years. I looked for night-time monitors but couldn’t find anything suitable. I am an engineer by training and

6 RESEARCH QUARTERLY | JUNE 2019 I AM AN ENGINEER BY TRAINING“ AND PUT THOSE SKILLS TO USE. – CHARLES ANDERSON ”

How does the system seizure control and independence. If you are considering seizure currently work? At that point we had tried all detection devices, here are some SAMi uses a camera in the the available medications. After of the questions to think about: bedroom that works in complete doing the work-up at the epilepsy • What do you want the device darkness. The video data is sent to center and determining that he to do once a possible seizure an iOS device (iPhone/iPad/iPod) was a good candidate he had a is detected? that is running an app I wrote temporal lobe resection. He is • What is your living situation, to look for unusual movement. still on medications, but he is and does it fit with the device The parent or other care-partner living a seizure free life. requirements? typically has this on a nightstand by their bed. While the app is Learn more about • Do you want to use the device running it displays a clock. When the journey through outside of the home? unusual movement is detected an epilepsy surgery on • Do you want data from the alarm is sounded and the iPhone epilepsy.com/surgery device to be shared with other turns on the live video and audio people? feed from the room where the Visit The Brain • How much does the device person with epilepsy is. Moreover, Recovery Project, a cost? all of these events are recorded, nonprofit focused • Are there any downsides to time-stamped and archived for on helping navigate using the device? your review later as well. Since the decisions around • Can the device prevent sudden the award and the improvements epilepsy surgery and unexpected death in epilepsy in design, we have sold around support after surgery. (SUDEP) or any of the factors 6,000 of these devices around that may lead to SUDEP? the world. Is there anything else that you “It [SAMi] makes sleep possible would like to add? When considering a device, please for us,” said Leslie D. on the I wanted to thank the Epilepsy talk to a healthcare professional. Epilepsy Foundation Facebook Foundation for the early support If you need assistance or want page. through the Epilepsy Therapy to learn more about devices, Project. But more importantly, I the DannyDid Foundation is an How is your son doing now? wanted to stress the importance excellent resource. My son is seizure free! In his last of monitoring for night time year of high school, he decided the seizures. Whether you use our risk of surgery was outweighed system or another system, please by the benefit of having more consider using one!

PEOPLE IN PEOPLE PEOPLE WILL BE THE UNITED STATES WILL HAVE A DIAGNOSED WITH LIVE WITH EPILEPSY IN SEIZURE IN IN EPILEPSY IN 3.4 AND SEIZURES 1 10THEIR LIFETIME 1 26 THEIR LIFETIME MILLION

RESEARCH QUARTERLY | JUNE 2019 7 INNOVATOR SPOTLIGHT 2 #USEYOURBRAIN

Greg Mayes is the president, What is your personal What was one of the hardest CEO, and founder of Engage connection to epilepsy? aspects of watching your Therapeutics. Engage Therapeutics In the summer of 2014, I was on son’s seizures? is an epilepsy company founded vacation with my family. We were The rules of seizure first aid are in 2017 to clinically develop at the breakfast table when my simple: stay calm, time the seizure, and progress a product called son dropped his face in the bowl keep him safe, and stay with staccato alprazolam. Staccato of cereal. At first, I thought he him until he is alert again. Most alprazolam has the opportunity to was horse playing, then I realized seizures end in a few minutes, become the first FDA-approved he might be choking. It was his but those can be the longest few inhaler therapy to abort an active first generalized seizure minutes of your life. I knew that seizure. Greg is also personally if the seizure lasted longer than connected to epilepsy. We sat Had you ever witnessed a 5 minutes, I needed to call 911. down with Greg to learn a little seizure before? But other than that, there was bit more about his connection Looking back, my son had nothing I really could do. to epilepsy and what motivates probably had other seizures. him to do the work that he does. We always assumed that seizures Go to epilepsy.com/ were the type shown in the firstaid to learn about movies, the tonic-clonic motor seizure safety movements. We hadn’t realized the many different ways that a When my son went on school seizure could manifest. trips, I had to check the box that said that there is a medical Go to epilepsy.com/ condition the school field trip learn/types-seizures organizers needed to know about. to learn more about I would always get the question about whether I could send some rescue treatment along. How is your son doing now? But there wasn’t a viable option. 2014 was a scary year for us, with We didn’t have an EpiPen option three big seizure events resulting for epilepsy. That is what excites in emergency situations. His me about Engage Therapeutics. seizures are currently controlled When I heard about this product, I with medications, but we all live in wanted to help bring it to market. fear of the seizures coming back We need rescue therapy options

8 RESEARCH QUARTERLY | JUNE 2019 I WANTED TO USE MY“ EXPERIENCE AND EXPERTISE TO HELP THE EPILEPSY COMMUNITY IN SOME WAY. – GREG MAYES”

Go to www. What has been your biggest Is there anything else that you engagetherapeutics. challenge so far at Engage would like to add? com to learn more Therapeutics? I wanted to genuinely thank We want sound science to ensure the Epilepsy Foundation. It about the product and that the product works before it was through the Foundation the trial. gets to market. For this, we need leadership that I got connected to complete the clinical trials. to the resources our family What experience do you bring Recruitment can be really tough needed. It was also through the to the epilepsy space? because we need participants Foundation, that I was able to I had been a pharma executive who are known to have weekly learn about potential business for over 20 years. My entire seizures that last a few minutes. investment opportunities and career was in the business and This is critical, because we want the licensing opportunity with legal departments of life science to be positive that our inhaler this product. More than half of companies. In 2014, I was working is working and stopping the the Engage team is personally in the cancer field. It was extremely seizures. We want to test this affected by epilepsy and we are rewarding to be in that space. But on over 120 individuals to be in full support of the Foundation’s with my son, watching his seizures, confident in the product. We are mission, both nationally and I felt so helpless. I wanted to use now halfway through recruitment locally. The Engage team is my experience and expertise to and have 42 sites around the US, actively participating in many help the epilepsy community in Caribbean, Australia and Canada of the Foundation’s sponsored some way. Walks to END EPILEPSY®. So, if you are listening and attending, please come by and see us at the booth to learn more about how you can help bring this important product to market.

OFTEN GOES IS THE 4TH MOST COMMON UNDIAGNOSED OR NEUROLOGICAL DISEASE AND EPILEPSYIS MISDIAGNOSED. EPILEPSY AFFECTS PEOPLE OF ALL AGES.

RESEARCH QUARTERLY | JUNE 2019 9 NEXTGEN SCIENTIST AWARDS To answer this question, Dr. Esmaeili’s will be mining data from a data repository from the We are proud to partner with American epilepsy monitoring unit of 5 major academic Epilepsy Society (AES), to attract the best epilepsy centers to understand the range of and the brightest in the field. Since the 1960s, characteristics of the brain activity and heartrate the Epilepsy Foundation has supported the variability post-seizure, and whether there are any significant factors in either of these two careers of over 3,000 researchers. measurements in confirmed SUDEP cases. This work could highlight physiological factors that indicate who is at higher risk of SUDEP. AES/EF CLINICAL RESEARCH & TRAINING FELLOWSHIP : BEHNAZ ESMAEILI MD AES/EF JUNIOR INVESTIGATOR RESEARCH TITLE: INTRACRANIAL EEG SUPPRESSION AWARD: WILLIAM NOBIS MD, PHD AND HEART RATE VARIABILITY IN EPILEPSY TITLE: THE ROLE OF THE EXTENDED INSTITUTION: BRIGHAM AND WOMEN’S AMYGDALA IN RESPIRATORY CONTROL HOSPITAL AND SUDEP INSTITUTION: VANDERBILT UNIVERSITY MEDICAL CENTER

SUDEP is the sudden, unexpected death of someone with epilepsy, who was otherwise healthy. Sudden unexpected death in epilepsy (SUDEP) In SUDEP cases, no other cause of death is found is the leading cause of death in people with when an autopsy is done. Each year, about 1 in uncontrolled seizures. Seizure-related apneas 1,000 people with epilepsy die from SUDEP. The (cessation of breathing during a seizure) are being mechanism(s) of SUDEP are still under intense observed in epilepsy units where respiratory investigation by researchers in the US and across status is consistently monitored. When SUDEP the world. has occurred in a healthcare setting, apnea has The most consistent risk factor for SUDEP is frequent been observed prior to the terminal cardiac generalized tonic-clonic (GTC) seizures. Certain arrhythmias. This suggests that SUDEP might be individuals experience a dramatic suppression of a lethal combination of a seizure related apnea brain activity after a GTC seizure. This phenomenon along with impaired consciousness in the individual is also linked to the altered state of consciousness post-seizure. post-seizure, which can last between 5 to 30 In previous work, Dr. Nobis established that an minutes. In addition to the change in brain area of the brain known as the extended amygdala, activity, clinicians have also observed decreased which when stimulated causes apnea. Dr. Nobis heartrate variability in individuals post seizure. In hypothesizes that this region or the parabrachial a healthy heartbeat, you would experience healthy nucleus, another area implicated in respiratory irregularities. For example, if you place a finger control, may be activated during a seizure and on your pulse, you would notice that your pulse thus cause the observed seizure-induced apneas. can change based on how you breath (exhale Using animal models that study SUDEP, he will versus inhale). These heart rate variabilities are test whether and how these brain regions are dampened post-seizure. The question remains impacted during a seizure, and how this can about whether the characteristics of the brain impact respiratory control. Understanding this activity suppression and the decrease in heartrate pathway and its role could open up new prevention variability post-seizure could be indicators of strategies for those at high risk of SUDEP. increased risk for SUDEP.

10 RESEARCH QUARTERLY | JUNE 2019 AES/EF JUNIOR UPCOMING RESEARCH GRANTS INVESTIGATOR RESEARCH AWARD: ALICIA GUEMEZ SUDEP BIOMARKER CHALLENGE GAMBOA PHD Submissions open now TITLE: UNCOVERING Prize for $800,000 ALTERED CONNECTIVITY IN EPILEPSY FOUNDATION MY BRAIN MAP EPILEPSY DUE TO SOMATIC MUTATIONS RESEARCH GRANTS Extended deadline: Letters of Intent due INSTITUTION: NORTHWESTERN July 26, 2019 UNIVERSITY Award up to $200,000

EPILEPSY FOUNDATION SHARK TANK A somatic mutation is a genetic mutation that AWARDS occurs as a cell divides in the developing body. Letters of Intent due September 16, 2019 If there is a genetic mutation that occurs during Award up to $200,000 the division, this would be contained to the cell that the mutation occurred in and the other cells AES EARLY CAREER DEVELOPMENT AWARDS that this cell helped to create afterwards. There is Letters of Intent due October 1, 2019 evidence of somatic diversity in the brain, which Award up to $50,000 over 1 year means that specific brain cell populations have a genetic mutation in their DNA not associated with EPILEPSY FOUNDATION CLINICAL RESEARCH other brain cells or organs in the body. Some of TRAINING APPRENTICESHIP AWARDS Applications due October 1, 2019 these somatic mutations in the developing brain Award up to $35,000 for three months of have been linked to focal cortical malformations research spread out throughout the year associated with pediatric drug-resistant epilepsy. To better understand how somatic mutations SUSAN S. SPENCER CLINICAL RESEARCH could impact epilepsy and brain circuits, Dr. FELLOWSHIP Gamboa has created a mouse model that causes Applications due October 1, 2019 brain cell specific genetic mutations that activate Award up to $150,000 over 2 year the mTOR pathway during cortical development. There are many studies that observe a frequent EPILEPSY FOUNDATION NEW THERAPY hyperactivation of mTOR signaling in epilepsy. COMMERCIALIZATION GRANTS For example, seizures associated with Tuberous Information on deadline coming soon Sclerosis, a rare genetic epilepsy syndrome, Award up to $200,000 is treated by mTOR inhibitors. In this research proposal, she will explore how somatic mutations in the mTOR pathway in a contained population of Do you have questions or a research neurons result in network abnormalities that lead funding opportunity to share? to epilepsy. The disease mechanisms that arise from this research could lay the groundwork for Email [email protected] new therapeutic approaches. Want to donate funds to research? Go to: donate.epilepsy.com/donate- research

SUDEP Learn more about SUDEP by going to the SUDEP Institute, a program within the Epilepsy Foundation at epilepsy.com/SUDEP or SUDEP Institute/Epilepsy Foundation on Facebook. The Institute promotes and supports research to eradicate SUDEP, brings awareness and education around it and supports the bereaved.

RESEARCH QUARTERLY | JUNE 2019 11 EPILEPSY LEARNING HEALTHCARE SYSTEM (ELHS)

network. New ideas are generated and -Do Our Story -Study- families are integrated at every step to drivein Numbers (ELHS) is looking to change that. insight.

WithPARTNERING the support of TO the IMPROVE Epilepsy OUTCOMESELHS strives to improve quality of life and to reduce or eliminate seizures for all The Epilepsy Learning Healthcare System (ELHS) 6 is building a quality improvement and research network dedicated to improving outcomes for children and adults with epilepsy. 2 Confirmed clinical sites now include: • Barrow Neurologic Institute (AZ) • Beth Israel Lahey Health (MA) 3 • Children’s Hospital of Atlanta (GA) • Children’s Hospital of Philadelphia (PA) • Partner’s Healthcare (MA): Brigham & Women’s and Massachusetts General Hospitals 12 • Penn State Hershey Children’s Hospital (PA) The 2nd ELHS Learning Session took place on % Monday May 6th in Philadelphia, PA. Ms. Monika 30 Jones (The Brain Recovery Project Childhood Epilepsy Surgery Foundation) and Ms. Priscilla Kobi (Epilepsy Foundation) graciously provided 71% Ignite Talks sharing their experiences with epilepsy - focusing the attendees on the reason for the work. Site teams (made up of clinicians and patient & family partners from the Community Engagement 2 Core) are currently working on improving seizure documentation both on the clinician and patient sides. The next phase of work will focus on medication 31 adherence (a key driver of seizure control) – this will begin with an evidence review and roll-out of the next change package at the October 27th ELHS Learning Session in Charlotte, NC. Areas of Focus For more information on the Community Engagement Core of the ELHS please contact Ms. Alison Kukla. Work is currently underway to connect REN and other organizations, as well as local Epilepsy Foundation teams, with clinical sites as they come on board – please share with your networks the news of this opportunity!

For more information on the Clinical Core, please contact Dr. Kathleen Farrell – [email protected]

12 RESEARCH QUARTERLY | JUNE 2019 FDA: BREAKING NEWS! MY SEIZURE GAUGE

In May, the U.S. Food and Drug Administration PUBLICATION ALERT approved the use of NAYZILAM®(midazolam) We are getting better and better at forecasting nasal spray for use in children age 12 and over the weather. What if we could do the same with and adults with epilepsy. seizures? The Epilepsy Foundation My Seizure Gauge initiative is leading an effort to create • Nayzilam is a rescue therapy for acute (immediate, an individualized seizure gauge that will allow a short-term) treatment of intermittent, stereotypic person with epilepsy to monitor the likelihood of episodes of frequent seizure activity. This means a seizure on a daily basis. For this effort, we are that the medicine can be used to treat seizure promoting user-centered design concepts and clusters, bouts of increased seizures, or acute asking our community what they would want repetitive seizures. in a hypothetical seizure forecasting device. • It can be given by a non-medical person outside For this effort, we created 18 prototype device of a hospital setting – when a person needs it! descriptions that systematically varied across six • It’s a nasal spray that can be given easily by attributes: seizure forecasting probability, seizure the person with epilepsy between seizures. Or forecasting range, inaccuracy of forecasting, it can be given by someone else to a person amount of time required to use the device, how during a seizure. the device is worn, and cost. Respondents of the • Nayzilam (midazolam) is from a group of drugs survey indicated what would be the best and worst called benzodiazepines. It is very good at stopping features of the device and whether they would seizures quickly when used intermittently or “as use the prototype if it existed. Our survey findings needed” for specific situations. were recently published and extend previous calls • It is NOT approved as a seizure medicine to be for seizure forecasting devices by demonstrating used on a daily basis. And it should not take the the value that they might provide to patients and place of a person’s usual seizure medication. caregivers affected by epilepsy and the feature that might be most and least desirable. In addition to guiding device development, the data can help inform regulatory decisions makers. To review RESCUE THERAPIES the article, click here. To learn more about the CAN BE CRITICAL My Seizure Gauge Initiative go to www.epilepsy. com/myseizuregauge TO HELP STOP PERIODS OF SEIZURES THAT COULD LEAD TO SEIZURE EMERGENCIES, HOSPITALIZATIONS AND EARLY DEATH

EPILEPSY LIFETIME ACCELERATOR AWARD The Epilepsy Foundation awarded the Epilepsy Lifetime Accelerator Award to Professor Martin J. Brodie, M.D., president of the International Bureau for Epilepsy. Dr. Brodie has been involved in epilepsy drug development for more than 30 years and was principal investigator on numerous trials that brought new therapies to market. He was an innovator of novel trial designs and is arguably the most recognized speaker on new anti-epileptic drugs in the world.

RESEARCH QUARTERLY | JUNE 2019 13 THE SUDEP INSTITUTE Biomarker CHALLENGES TO DATE: Challenge 1: Advocacy Campaign Empowering people with epilepsy, Challenge $15k awarded Challenge 2: Self Management Tools

Each year, more than 1 out of 1,000 people EpSMon (Epilepsy Self-Management) with epilepsy die from sudden unexpected mobile app created death in epilepsy (SUDEP). If seizures are Challenge 3: uncontrolled, the risk of SUDEP increases to more than 1 out of 150. SUDEP is the seizures, $75k awarded leading cause of death in young adults Challenge 4: Bringing Biomarkers to with uncontrolled seizures. Clinic

biomarkers of SUDEP Among the 65 million people worldwide living with epilepsy, Milestone 1 Project plan, $40K awarded

Milestone 2 Proof of concept, $80K awarded

Milestone 3 people at risk for SUDEP. If we can know who is at risk, we can pr Current Challenge!

challenges allow us to take advantage of The Final Milestone of our Final Challenge is interdisciplinary approaches and

PLEASE Through combining and CONSIDER body, metabolic, physiological, or something else DONATING and most valuable to funding the

The winning biomarker will be easily and safely Please, help us will be a win for ALL reach for the stars who have a loved supported. in this winning one living with epilepsy. prevent), be consistently associated with SUDEP us save lives. or life-threatening seizures, and will drive human

Learn more go to epilepsy.com/sudep

03/2019 880SBC

14 RESEARCH QUARTERLY | JUNE 2019 CLINICAL TRIALS PORTAL LISTINGS:

Clinical trials are the way new causing intractable epilepsy in EPILEPSY FOUNDATION’S treatments are tested for safety adults 18 to 80 years old. The study HUMAN EPILEPSY PROJECT and effectiveness before being will evaluate the effectiveness and (HEP2): RESISTANT FOCAL SEIZURES STUDY approved and made available to safety of an investigational device people with epilepsy. that uses ultrasound or sound This study, the Human Epilepsy waves from outside the head to Project 2: Resistant Focal Seizures treat seizures that are not well (HEP2) is designed to better Rare Epilepsy controlled by medication and are understand the challenges of Syndrome Trials due to a small growth of abnormal living with focal seizures that do cells in the middle of the brain, not respond to medication and CANNABIDIOL AS AN ADD- determine biomarkers of epilepsy ON THERAPY IN TUBEROUS most commonly hypothalamic severity and treatment response SCLEROSIS COMPLEX hamartomas. This study is looking at how effective and safe cannabidiol PERAMPANEL STUDY FOR Focal or Generalized (CBD) is in people 1 year to 65 INFANTS WITH EPILEPSY Seizures Trials years old living with Tuberous This clinical research study is Stereotactic Laser Ablation For Sclerosis Complex (TSC). CBD is being done to learn more about (SLATE) given in addition to their current the safety of Perampanel (E2007), anti-seizure medications. the study drug, and how well it’s This study is looking at the safety tolerated in infants, from 1 month and efficacy of MRI-guided laser to less than 24 months old (<2 ablation therapy with Visualase™ PREVENTING EPILEPSY USING years), who have epilepsy. (laser ablation may also be called VIGABATRIN IN INFANTS WITH laser interstitial thermal therapy TUBEROUS SCLEROSIS COMPLEX or LITT) for seizures coming from This Phase IIb trial will test Focal (Partial-Onset) the temporal lobe in people who whether earlier treatment Seizures Trials are taking seizure medicines. versus standard treatment ESLICARBAZEPINE ACETATE Effectiveness of Inhaled Staccato with vigabatrin in infants with (ESL) AS FIRST OR LATER Alprazolam in Treating an Episode tuberous sclerosis complex (TSC) ADD-ON THERAPY FOR THE of Focal or Generalized Seizures will have a positive impact on TREATMENT OF PARTIAL- developmental outcomes at ONSET SEIZURES A new clinical trial is looking at how 24 months of age. It also tests This study is looking at how effective and safe orally-inhaled whether early treatment prevents effective and safe eslicarbazepine alprazolam (also known as STAP- or lowers the risk of developing acetate (also known as ESL) is in 001) is in people 18 years of age infantile spasms and refractory people 18 years of age or older or older with focal or generalized seizures. It is a randomized, with partial-onset (focal) seizures, epilepsy when given at the time double-blind, placebo-controlled when it is added to their current of a seizure episode. This study is clinical trial design. Infants under anti-seizure medication(s). commonly referred to as StATEs the age of 6 months diagnosed (Staccato Alprazolam Terminates with TSC but without history of PFIZER A0081096: LOOKING Epilepsy Seizures). seizures or infantile spasms may FOR CHANGES IN EYESIGHT be eligible. FROM USING PREGABALIN Go to epilepsy.com/clinical_trials This study will look at people to learn more. between 18-65 years old, taking FOCUSED ULTRASOUND FOR TREATMENT OF EPILEPSY their own anti-seizure medications in addition to either the study The University of Virginia drug (Pregabalin) or a placebo. Comprehensive Epilepsy Program The aim is to look for changes is conducting a research study in eyesight. on the use of focused ultrasound to treat deep lesions in the brain

RESEARCH QUARTERLY | JUNE 2019 15 UPCOMING CONFERENCES

2019 DUP15Q ALLIANCE SCIENTIFIC 4TH INTERNATIONAL SYMPOSIUM ON SYMPOSIUM HYPOTHALAMIC HAMARTOMAS July 17-18, 2019, Houston TX September 12-14, 2019, Washington DC https://www.dup15q.org/events/scientific- http://www.hopeforhh.org/4th-international- conferences/2019-dup15q-alliance-scientific- symposium-on-hypothalamic-hamartomas/ symposium/ PARK CITY EPILEPSY MEETING BRAIN RECOVERY PROJECT October 6-8, 2019, Park City, UT July 19-20, 2019, Cleveland OH http://www.parkcityepilepsymeeting.com https://www.brainrecoveryproject.org/parents/ CHILD NEUROLOGY SOCIETY 48TH ANNUAL programs/conferences/2019conference/ MEETING 3RD FAMILIESCN2A FAMILY AND October 23-26, Charlotte, NC PROFESSIONAL CONFERENCE https://www.childneurologysociety.org/ August 1-3, 2019, University of Washington, meetings/future-cns-annual-meetings Seattle, WA BRIDGE THE GAP FAMILY MEET UP https://www.scn2a.org/conference.html November 9-10, 2019, Johns Hopkins School SUNFLOWER SYNDROME FAMILY of Medicine and Kennedy Krieger Institute, CONFERENCE Baltimore MD August 4, 2019, Massachusetts General Hospital https://bridgesyngap.org/ https://because.massgeneral.org/event/ syngapinternationalconference/attachment/ sunflower-syndrome-family-symposium/ baltimore-meetup/ e182170 AMERICAN EPILEPSY SOCIETY ANNUAL BRIDGE SYNGAP FAMILY MEET UP MEETING 2019 August 16-17, 2019, Baylor College of Medicine- December 6-10, 2019, Baltimore, MD Texas Children’s Hospital, Houston, Tx https://meeting.aesnet.org/about/future- https://bridgesyngap.org/houston-family- meetings meetup/

INTERNATIONAL CONFERENCE FOR TECHNOLOGY AND ANALYSIS OF SEIZURES, 2019 (ICTALS2019). September 2-5, 2019, University of Exeter, UK http://www.exeter.ac.uk/livingsystems/ newsandevents/events/ictals2019/

5TH INTERNATIONAL LAFORA EPILEPSY WORKSHOP September 8-10, 2019, Alcala, Spain Contact [email protected]

PIPELINE CONFERENCE 2020 February 20-22, 2020, Santa Clara, CA https://www.epilepsy.com/pipeline2020

Have a conference that you want to share? Email [email protected]

16 RESEARCH QUARTERLY | JUNE 2019