- CURE Epilepsy is the leading non-profit organization focused on funding research to find cures for epilepsy.
- To achieve our mission, CURE Epilepsy created grant mechanisms to support research to understand the basic biological mechanisms or foundations of what causes seizures that become epilepsy as well as awards for pre-clinical research and more.
- The Taking Flight Award was created to support epilepsy investigators early in their careers to develop a research focus separate from their mentor’s.
- This Discovery highlights three Taking Flight awardees who received grants for diverse projects, ranging from work on sudden unexpected death in epilepsy (SUDEP) to mapping epileptic brain networks, to an exploration of circadian function as a potential mechanism and a therapeutic target for epilepsy.
- The three awardees are Dr. William Nobis from Vanderbilt University Medical Center, Dr. Flavia Vitale from The University of Pennsylvania, and Dr. Cristina Reschke at the Royal College of Surgeons in Ireland. These awardees share their motivations for pursuing epilepsy research as a career, the importance of the CURE Epilepsy Taking Flight in their careers, and the impact they hope to have in the epilepsy community.
Epilepsy is one of the most common neurological disorders and affects 65 million people worldwide  and 3.4 million Americans . Epilepsy can impact a person at any point in their lifetime, regardless of age, demographics, race, or socioeconomics. Those who live with epilepsy can face a lifetime of challenges. CURE Epilepsy’s mission is to find a cure for epilepsy, by promoting and funding patient-focused research, CURE Epilepsy has developed a variety of granting mechanisms , including the Taking Flight Award. This one-year, $100,000 grant is meant to fund studies that will provide new insights into epilepsy, its prevention, and cures. An additional goal of the Taking Flight Award is to foster scientific independence of early career investigators and provide them with the means to collect the necessary data to apply for subsequent funding, thus further advancing their career in epilepsy research.
Through 2021, CURE Epilepsy has funded 48 early career scientists through the Taking Flight Award, supporting them on their path to research independence. Recently, we spoke with three Taking Flight awardees about their research, the impact that receiving the Taking Flight Award had on their research and their vision for the future of their research. The three awardees and their projects were: Dr. William Nobis at Vanderbilt University Medical Center who studied a part of the brain called the amygdala and its role in sudden unexpected death in epilepsy (SUDEP); Dr. Flavia Vitale at The University of Pennsylvania who explored a technique to accurately map epileptic brain networks; and Dr. Cristina Reschke at the Royal College of Surgeons in Ireland, who examined the role of the circadian function in epilepsy.
The awardees noted varying inspirations to pursue the field of epilepsy research. For example, Dr. Nobis mentioned, “I have always been interested in neuroscience research, my initial motivation for training to be a physician-scientist was my experience with my grandmother and Alzheimer’s disease. During my residency training in neurology, I had exposure to epilepsy patients and experience with epileptologists, and I liked the impact you could have on patients’ lives by controlling seizures.” Dr. Nobis continues to be inspired by the patients he aims to serve. He says, “I want to do research that has the opportunity to make an impact on my patients’ lives – this is something that is within reach for epilepsy researchers. We have come far with controlling epilepsy but there are still so many people impacted by seizures.
Controlling epilepsy and preventing SUDEP are both interesting problems that will involve cutting edge circuit-based science and are also of immense importance and impact for the lives of our patients.” Previous research on SUDEP had shown that difficulties in breathing (respiratory depression) could lead to deficits in heart function, ultimately leading to death. To understand this process better, Dr. Nobis’ team analyzed intracranial electroencephalograph (EEG), i.e., electrical signals from deep within the brain, and combined this with the measurement of breathing. They found a specific role of the amygdala and the brainstem in respiratory depression during seizures. The discovery that this circuit may play a role in SUDEP means that in the future, we may be able to target it with interventions to prevent SUDEP.
According to Dr. Nobis, the Taking Flight Award gave him the capability to commit full-time to the SUDEP research, which had been a side project that he was working on in his mentor’s lab. He was able to publish his studies and take the next step in his career by accepting a position at Vanderbilt University Medical Center. Subsequent mentored career-development awards helped him launch his research program centered on the physiological mechanisms of SUDEP. Looking into the future, Dr. Nobis commended the epilepsy research community with these words, “I love the epilepsy research community; I have not been around a group of more earnest and supportive group of scientists that are dedicated to improving the treatment of epilepsy patients. To do something that will improve the lives of epilepsy patients and work towards the goal of no SUDEP, no seizures, and no side effects.”
The basis for Dr. Vitale’s research is the premise that epilepsy arises from disrupted brain networks. To properly treat seizure-related conditions, it is important to map these networks as precisely as possible, but current methods of mapping epileptic neuronal networks do not provide the fine level of detail that is necessary. As part of Dr. Vitale’s Taking Flight research project, she developed miniature, flexible electrodes that could be controlled independently after they were implanted in the brain. This technology has already shown success in detecting seizures in mice [6,7], and it is envisioned that this work of detecting seizure activity in experimental animals could ultimately lead to technologies to map epileptic networks in patients in a highly precise manner.
Speaking to her motivation, Dr. Vitale, was interested in joining a multidisciplinary team that “brings together engineers, clinicians, and neuroscientists to develop novel technological and therapeutic approaches to understand, diagnose, and treat neurological disorders, and in particular epilepsy.” Dr. Vitale found that working closely with clinicians and surgeons whose mission is to fight epilepsy, made her realize how engineers developing new devices, algorithms, modeling, and analysis tools can play a key role in supporting clinicians in their decision-making and provide them with more accurate and effective tools to diagnose and treat their patients. She also mentioned that the personal stories from patients and families reinforced her decision to start a career in neuro-engineering for epilepsy research.
Dr. Vitale describes the Taking Flight Award as an “inflection point” in her career, as the award enabled her to start her lab at the University of Pennsylvania. In her words, “this award jumpstarted my research program in epilepsy research and helped me to gather key preliminary data that later supported successful grant applications and publications. Finally, the award provided recognition among the epilepsy research community and helped me establish new fruitful collaborations.” She summarizes her views on epilepsy research as, “Our mission is to ultimately translate our findings and technological innovations to patients. With more precise and safer electrodes, it will be easier to find and remove the areas of the brain where seizures originate, which has been shown to improve seizure-free rates. We are also developing easier-to-use, portable, and low-cost non-invasive brain monitoring systems to improve access and quality epilepsy care in low-resource settings and for at-home monitoring. Such technologies will offer more accurate data for diagnosis and therapy and reduce the burden of travel to patients in remote areas.”
Dr. Reschke’s work focuses on how circadian rhythms may impact epilepsy.[9,11] Previous studies have hypothesized a link between epilepsy and the 24-hour biological rhythms present in humans that are called “circadian rhythms.” Dr. Reschke’s award, funded by The Cameron Boyce Foundation, aims to explore whether the mechanisms that control circadian rhythms are involved in the process of epileptogenesis (the process by which a non-epileptic circuit is transformed into an epileptic circuit). She will also develop a gene therapy approach in mice to see whether restoring a gene involved in circadian rhythms can halt epileptogenesis.[9,11]
Dr. Reschke emphasized the excitement of discovery and the patient-centeredness of research as two main reasons she was attracted to working in epilepsy. “If we understand a bit more about the brain, we can develop focused and tailored approaches to epilepsy and accompanying comorbidities.” To her, while the science and research are extremely interesting, the possibility of impacting people with epilepsy, “makes the long hours worthwhile.”
Dr. Reschke also found her independence as a researcher thanks to the Taking Flight Award. The award allowed her to obtain, first, a temporary, and later, a permanent position at the Royal College of Surgeons in Ireland. She was able to secure lab space and personnel to do the work. The Taking Flight Award, in her words, “was extremely important and instrumental in establishing my career in epilepsy in academia.” In addition to the support for research, the award also gave her international recognition and helped her enhance her professional networks. Leveraging her research, recognition, and networks, Dr. Reschke is heavily involved in advocacy and education as well. She feels that “communicating research to patients’ families and caregivers is crucial,” and she feels that it is critical to put her clinical work into practice. She is also passionate about educating the next generation of epilepsy researchers by promoting training and fellowships to give them, “the opportunities that I have; to give them a chance to work on research that is deeply meaningful.”
The Taking Flight Awards have deeply impacted the grantees, and through them, numerous people that are affected by epilepsy every day. Awardees cited the capacity to contribute to scientific excellence while having a positive impact on patients with epilepsy and their caregivers as the most rewarding aspect of the award. The money granted by CURE Epilepsy to the researchers to gain scientific independence, develop new techniques, and discover novel mechanisms of epileptogenesis will help the organization achieve our goal of a world without epilepsy.
- Ngugi AK, Bottomley C, Kleinschmidt I, Sander JW, Newton CR. Estimation of the burden of active and lifetime epilepsy: a meta-analytic approach Epilepsia. 2010 May;51:883-890.
- National and State Estimates of the Numbers of Adults and Children with Active Epilepsy — United States, 2015.
- CURE Epilepsy: Grant Opportunities Available at: https://www.cureepilepsy.org/grants-program/. Accessed November 11
- CURE Epilepsy Taking Flight award Available at: https://www.cureepilepsy.org/wp-content/uploads/2022/10/2023-Taking-Flight-Award-LOI-Full-Propsal-Guidelines.pdf. Accessed November 11
- Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A, et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study Lancet Neurol. 2013 Oct;12:966-977.
- Nobis WP, González Otárula KA, Templer JW, Gerard EE, VanHaerents S, Lane G, et al. The effect of seizure spread to the amygdala on respiration and onset of ictal central apnea J Neurosurg. 2019 Apr 5;132:1313-1323.
- Department of Neurology; William P. Nobis, MD, Ph.D. Available at: https://www.vumc.org/neurology/person/william-p-nobis-md-phd. Accessed November 11
- Mulcahey PJ, Chen Y, Driscoll N, Murphy BB, Dickens OO, Johnson ATC, et al. Multimodal, Multiscale Insights into Hippocampal Seizures Enabled by Transparent, Graphene-Based Microelectrode Arrays eNeuro. 2022 May-Jun;9.
- Driscoll N, Rosch RE, Murphy BB, Ashourvan A, Vishnubhotla R, Dickens OO, et al. Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale Commun Biol. 2021 Jan 29;4:136.
- Flavia Vitale, Ph.D.; Penn Medicine Available at: https://www.med.upenn.edu/apps/faculty/index.php/g324/p8887287. Accessed November 11
- Restoration of Circadian Function as a Novel Therapy for Epilepsy. Available at: https://www.cureepilepsy.org/grant_type/restoration-of-circadian-function-as-a-novel-therapy-for-epilepsy/. Accessed November 11.
- Jin B, Aung T, Geng Y, Wang S. Epilepsy and Its Interaction With Sleep and Circadian Rhythm Front Neurol. 2020;11:327.