OBJECTIVE: The Epilepsy Genetics Initiative (EGI) was formed in 2014 to create a centrally managed database of clinically generated exome sequence data. EGI performs systematic research-based reanalysis to identify new molecular diagnoses that were not possible at the time of initial sequencing and to aid in novel gene discovery. Herein researchers report on the efficacy of this approach 3 years after inception.
METHODS: One hundred sixty-six individuals with epilepsy who underwent diagnostic whole exome sequencing (WES) were enrolled, including 139 who had not received a genetic diagnosis. Sequence data were transferred to the EGI and periodically reevaluated on a research basis.
RESULTS: Eight new diagnoses were made as a result of updated annotations or the discovery of novel epilepsy genes after the initial diagnostic analysis was performed. In five additional cases, the team provided new evidence to support or contradict the likelihood of variant pathogenicity reported by the laboratory. One novel epilepsy gene was discovered through dual interrogation of research and clinically generated WES.
SIGNIFICANCE: EGI’s diagnosis rate of 5.8% represents a considerable increase in diagnostic yield and demonstrates the value of periodic reinterrogation of whole exome data. The initiative’s contributions to gene discovery underscore the importance of data sharing and the value of collaborative enterprises.
This past month, CURE attended the Research RoundTable for Epilepsy to provide input on clinical trial design. The roundtable focused on trials aiming to help individuals with rare, genetic forms of epilepsy.
Importantly, government and pharmaceutical representatives listened to patient representatives and clinicians, who gave their thoughts on clinical trial design. The hope of all attending was to optimize clinical trial design for maximum impact, efficiency, and validity, while addressing patient and caregiver needs.
Hearing feedback on the epilepsy research process from those directly affected is critical for getting vital treatments and therapies to those who need them most. These discussions are invaluable within the epilepsy community.
In addition to sharing information about this exciting discussion, this update highlights news and opportunities to engage with CURE, our partners, and the epilepsy community:
April 25: Webinar and Live Q&A on Transitioning from Pediatric to Adult Epilepsy Care
If your child has epilepsy, the transition of their care from a pediatric to adult neurologist is a critical time. In this month’s free webinar and live Q&A, discover how parents, patients, and doctors can plan the transition. Also, learn the established research guidelines which inform the transition care process. Register now to join us on Thursday, April 25 at 2:00PM CT.
The webinar is supported by the generosity of the BAND Foundation.
Survey: Help Improve Care for Children with Disruptive and Harmful Behaviors
Assist health care providers in better serving children with neurological conditions by participating in this survey of parents and caregivers developed by the Child Neurology Foundation (CNF). The survey closes on Wednesday, April 10.
The survey seeks feedback to better understand managing disruptive or harmful behavior in children with neurologic conditions, including epilepsy. The CNF will share anonymous information from this survey with health care providers, so they can better assist families.
Time is Running Out: Apply for a CURE Scholarship by April 15!
CURE is helping scholars become agents of change for the epilepsy community with Education Enrichment Fund (EEF) scholarships of up to $5,000. The deadline to apply for these scholarships is Monday, April 15.
EEF scholarships support coursework aiming to advance personal knowledge in epilepsy research, health education, awareness, or advocacy. This one-time scholarship is awarded to those living with epilepsy or to family members and caregivers of those impacted by epilepsy.
EEF scholarships are made possible by the generous support of Lundbeck.
Boston: Join us for a Day of Science and an Evening of Art
Two thought-provoking CURE events are heading to Boston! Join us on Friday, May 10 for the 1:26 The Art of Epilepsy reception and art exhibition. Then on Saturday, May 11, get your epilepsy questions answered by a panel of leading experts at the CURE Day of Science event.
1:26 The Art of Epilepsy is an evening of inspired artwork created by artists spanning the globe, linked by the common thread of epilepsy. Although every artists’ story is unique, the works become a collective force to combat the injustices, discrimination, and marginalization people with epilepsy face. 1:26 The Art of Epilepsy honors the work of Dr. Steven Schachter, Professor of Neurology at Harvard Medical School, and Dr. Kevin Staley, CURE Post-Traumatic Epilepsy Investigator and Chief of Pediatric Neurology at Massachusetts General Hospital.
On Saturday morning ask a panel of clinicians and epilepsy researchers your questions at CURE’s Day of Science. At this free event, panelists will field your questions on the latest research as it relates to new epilepsy treatment options, surgery, genetics, and more. After the panel, enjoy small-group discussions with physicians and researchers over a provided lunch.
Stay tuned: More Day of Science locations around the US will be announced soon!
These events are made possible thanks to the generous support of the BAND Foundation.
The Cotton Family: A Daughter’s Memory Inspires Epilepsy Research and Programming Funding
To honor the life of Vivian Cotton, who suffered from epilepsy and passed away at the young age of 18 months, Shery & David Cotton and Lisa & Michael Cotton have committed $2 million to benefit CURE and our initiatives to find a cure for epilepsy.
Vivian, Lisa and Michael’s daughter, was born prematurely, and as a result she suffered from epilepsy due to hydrocephaly. Vivian was a fighter from the very beginning, but despite all the treatments and medications available, her seizures were never controlled.
This significant gift will enhance a wide range of CURE activities and further energize development of innovative research and programming to one day lead to a cure for epilepsy. We’re so grateful to the Cottons for their legacy gift in memory of Vivian and are honored they believe in our mission to create a world without epilepsy through supporting research.
New Episodes: Seizing Life, a CURE Podcast
Catch up on the latest episodes of the CURE podcast Seizing Life! In March, we explored:
Chicago, IL (March 28, 2019) – Citizen’s United for Research in Epilepsy (CURE) is delighted to announce that Shery and David Cotton and Lisa and Michael Cotton have committed $2 million to benefit CURE and its initiatives to find a cure for epilepsy.
Since its inception in 1998, CURE has been at the forefront of the dramatic shift in the epilepsy research community from simply treating seizures to enhancing understanding of underlying mechanisms and causes, so that cures and preventative strategies can be found. CURE’s research program is cutting-edge, dynamic and responsive to new scientific opportunities and directions through both investigator-initiated grants and unprecedented scientific programs and initiatives.
Shery and David Cotton were the co-founders of Meridian Health Plan, a family owned company where Michael, their son, served as the COO. Shery, David, Lisa and Michael are active philanthropists and strong community supporters, especially in Detroit and their home town of Grosse Pointe, Michigan. The family has a very personal relationship with epilepsy and CURE. Four years ago, Lisa and Michael Cotton’s daughter, Vivian passed away at the young age of 18 months. Born prematurely, she suffered from epilepsy due to hydrocephaly. Vivian was a fighter from the very beginning, but despite all the treatments and medications available, her seizures continued. Since losing Vivian in 2015, Lisa and Michael have been actively contributing and fundraising for CURE, and Lisa was elected to the CURE board of directors in 2018. This significant gift will enhance a wide range of CURE activities and further energize development of innovative research and programming that will one day lead to a cure for epilepsy.
“We are immensely grateful to Shery, David, Lisa and Michael. Their family’s story touches so many in the epilepsy community,” said CURE founder Susan Axelrod. “Their compassion and generosity in the face of such devasting loss is truly inspiring and will help fuel discoveries in Vivian’s memory that will save others from suffering similar tragedies in the future.”
ABOUT CURE The mission of Citizens United for Research in Epilepsy (CURE) is to find a cure for epilepsy by promoting and funding patient-focused research. Since its inception in 1998, CURE has raised over $60 million to advance its goal of no seizures and no side effects. To date, CURE has awarded more than 220 cutting-edge research projects in 15 countries around the world. CURE is the leading non-governmental agency fully committed to funding research in epilepsy. For information about CURE, please visit our website at: www.CUREepilepsy.org or contact us at: info@CUREepilepsy.org.
CURE-funded researchers are using a novel technique to discover ways to predict patients at an increased risk of Sudden Unexpected Death in Epilepsy (SUDEP). Dr. Lori Isom, her team, and co-investigator Dr. Jack Parent at the University of Michigan are transforming skin cells from patients with developmental and epileptic encephalopathy (DEE) syndromes into induced pluripotent stem cells (iPSCs). The team then generates cardiac cells from the iPSCs which retain the patients’ exact genetic information. These unique, patient-specific cardiac cells are used as models to understand if DEE-associated genes play a role in causing heart abnormalities which may lead to SUDEP. The team also hopes to develop measurable indicators, known as biomarkers, of SUDEP risk.
Severe DEE syndromes, such as Dravet syndrome, are associated with a high incidence of SUDEP. It is estimated that up to 20% of patients with Dravet syndrome die from SUDEP.1 There is still much to be understood about the mechanisms of SUDEP and how to predict who is at risk for it.
Dravet syndrome and other DEEs are often associated with variants in genes, such as SCN1A, SCN1B, and SCN8A. These genes provide instructions to make sodium ion channels, which are very important proteins that help brain cells transmit electrical signals. The same genes are also expressed in the heart; thus, the team hypothesizes that any variants in these genes that disrupt electrical signaling in the brain would affect normal electrical function of the heart as well. In support of this hypothesis, the investigators’ previous work in mouse models of Dravet syndrome and DEEs showed that these mice exhibited irregular heartbeat, which in some cases preceded SUDEP-like events.2-4
In this CURE-funded project, the investigators expanded upon their previous work by testing their hypothesis in heart muscle cells called cardiac myocytes, generated in the laboratory from skin cells of patients with Dravet syndrome or other DEEs using iPSC technology. This Nobel Prize-winning technology involves obtaining skin or blood cells from patients and converting them to iPSCs. These are stem cells that can be converted into almost any specialized cell type in the body, such as heart, muscle, pancreatic, or neuronal cells. The cells are patient-specific, meaning they retain the unique genetic make-up of the patient they originated from, allowing investigators to study cell types which would otherwise be very difficult or impossible to obtain from a living patient.
Dr. Isom, Dr. Parent, and their colleagues previously used iPSC technology to generate heart muscle cells from four patients with variants in the SCN1A gene and found increased sodium currents and spontaneous contraction rates in these cells, suggesting cardiac electrical dysfunction.5 Cardiac abnormalities were subsequently found in the patient with the highest increase in sodium current.5 These data suggest that iPSC-cardiac cells may be useful models for identifying and developing biomarkers, such as increased sodium current, as indicators of SUDEP risk.
The investigators used the same technique to study variants in the SCN1B and SCN8A genes. The team observed that iPSC-cardiac myocytes derived from a patient with SCN1B Dravet syndrome had increased sodium currents similar to those seen in iPSC-cardiac myocytes from the patient with SCN1A Dravet syndrome, suggesting that variants in these two different genes could cause heart abnormalities through similar mechanisms. Preliminary data in iPSC-cardiac myocytes from patients with DEE caused by variants in SCN8A, suggest that these cells have altered beating rates but no change in sodium current, which is aligned with their observations in a mouse model with a variant in SCN8A.
Taken together, these results reveal mechanisms by which different epilepsy-related genes can affect heart function and SUDEP. Future research will investigate the impact of variants of a specific non-ion channel gene to see if it causes altered cardiac beating. Patient-specific iPSC cardiac myocytes are a very useful model to study SUDEP mechanisms and could be developed as diagnostic biomarkers to identify SUDEP risk in patients.
1 Cooper MS et al. Mortality in Dravet Syndrome. Epilepsy Res. 2016 Dec; 128:43-47. 2 Auerbach DS et al. Altered Cardiac Electrophysiology and SUDEP in a Model of Dravet Syndrome. PLoS One. 2013;8(10). 3 Lopez-Santiago LF et al. Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. J Mol Cell Cardiol. 2007;43(5):636-47. 4 Frasier CR et al. Cardiac arrhythmia in a mouse model of SCN8A Epileptic Encephalopathy. Proc Natl Acad Sci U S A. 2016; in press. 5 Frasier CR et al. Channelopathy as a SUDEP Biomarker in Dravet Syndrome Patient Derived Cardiac Myocytes. Stem Cell Reports. 2018 Sep 11;11(3):626-634.
Our Leaders in Epilepsy Research Webinar Series is back! You can discover research on family planning and epilepsy, in addition to learning strategies for minimizing risk to women and infants during pregnancy in our latest webinar: Epilepsy, Pregnancy, and Contraception.
Webinar: Transitioning from Pediatric to Adult Epilepsy Care
It is critical for patients, parents, and neurologists to have a plan while transitioning from pediatric to adult epilepsy care. During a free webinar and live Q&A on Thursday, April 25 at 2:00PM CT, learn about research-based guidelines for developing a transition care plan, as well as what factors to consider during the transition.
Bring your questions for the live Q&A! You can ask the presenter, Dr. Joseph Sirven, questions such as:
Is the transition of care plan dependent upon a patient’s epilepsy type?
Do treatment options change when a patient begins seeing an adult neurologist?
What research has been done into the effects of transition care on a patient’s lifestyle?
This webinar is supported by the generosity of the BAND Foundation.
The application deadline for the 2019 Education Enrichment Fund (EEF) scholarships is April 15. These scholarships cover up to $5,000 of each recipient’s tuition, books, and any other course-required materials.
Made possible by generous support from Lundbeck, this one-time scholarship is awarded to those living with epilepsy or to family members and caregivers of those impacted by epilepsy. The scholarship supports coursework aiming to advance personal knowledge in epilepsy research, health education, awareness, or advocacy.
Stay tuned: More Day of Science locations around the US will be announced soon!
These events are made possible thanks to the generous support of the BAND Foundation and Sunovion.
CURE Champion Spotlight: Lauren Nathan Raises Funds for a “Real-Life Princess” with Epilepsy
CURE Champion Lauren Nathan raised $2,600 after being inspired by little Adelaide Cervantes, who was diagnosed with Infantile Spasms at just 7 months of age. Lauren and her husband, Jeff, are good friends of Adelaide’s parents, Kelly and Miguel Cervantes. Seeing her friends battle epilepsy moved her to act.
To honor Adelaide, who Lauren calls a real-life princess, she signed up for the Disney Fairytale Challenge, determined to raise vital funds to support CURE. The 2-day challenge involves completing the Enchanted 10K followed by the Princess Half-Marathon, totaling 19.3 miles.
When training got tough, Lauren remembered the daily challenges Adelaide and the Cervantes family face. “To be inspired is really amazing. It can push you further and harder than you will ever even know,” said Lauren.
On February 22 and 23, she conquered both races in the intense Florida heat, raising epilepsy awareness and funds in honor of little princess Adelaide.
Join a global movement to promote epilepsy awareness for International Epilepsy Day on February 11! More than 120 countries participate, working to highlight the problems faced by those with epilepsy, their families, and caregivers. Read on to learn how you can support epilepsy research while spreading the word about how prolific epilepsy is.
A Mind Unraveled, a Memoir by Kurt Eichenwald: Journalist and New York Times bestselling author Kurt Eichenwald discusses living with intractable epilepsy, the discrimination he faced, and what inspired him to share his story.
Plus this month, look forward to an interview with CURE founder Susan Axelrod.
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Get Involved Online and In-Person for International Epilepsy Day
Join the CURE community in raising funds for research and spreading epilepsy awareness on International Epilepsy Day.
Set Up a Facebook Fundraiser: Ask your Facebook friends help you fund research to find a cure for epilepsy. Share why raising funds for epilepsy research is so critical and encourage people to donate! Click here for a detailed guide or set up your fundraiser now.
Spread Awareness on Social Media: Show your friends, family, and followers how widespread epilepsy is, as well as how vital better treatment options are to so many people around the world. Download and share stunning epilepsy statistics to your social media pages.
Visit Select Chicago Häagen-Dazs Shops: Attend Ice Cream for a CURE at Häagen-Dazs shops in Harlem Irving Plaza or Lincolnwood Town Center. When you donate to CURE, you’ll receive 10% off one item. Also, a portion of the day’s sales from each location will benefit CURE.
Houston: CURE Day of Science is Coming Your Way!
At the CURE Day of Science event in Houston, leading experts answer your questions about epilepsy. This free event on Saturday, March 30 gives those impacted by epilepsy and their families the chance to learn from researchers and physicians in an encouraging environment.
During Day of Science, a panel of epilepsy experts address audience questions and participate in small-group discussions over lunch with the attendees.
Join us for answers to questions, such as:
What targeted treatments have been developed due to the discovery of new epilepsy genes?
What factors must be considered when moving my child from pediatric to adult care?
What are the risks associated with epilepsy surgery?
What epilepsy drugs are currently in development and what types of epilepsy can they be prescribed to treat?
This event is made possible thanks to the generous support of the BAND Foundation and Sunovion.
Finding a carefree moment as a parent to a six-year-old and a three-year-old child can feel like a challenge. When your child is diagnosed with epilepsy, those crucial, carefree moments in a marriage come with additional stress and worry.
On the new CURE podcast, Seizing Life, this is one of the topics host Kelly Cervantes discusses with her husband, HAMILTON Chicago star Miguel Cervantes; the rare carefree moments, obstacles and triumphs in their marriage while supporting their daughter who has epilepsy.
Kelly and Miguel Cervantes’ daughter Adelaide had her first seizure when she was just 7-months old. Now fierce advocates for finding a cure, the Cervantes have learned how to adjust to life with Adelaide’s condition while discovering their partner’s strengths and weaknesses along the way.
“Parents are in such a different mental place when it’s not about just regular life things and it becomes about the health and livelihood of your child,” says Miguel Cervantes in an inaugural episode. “Even in our carefree moments, in the back of our minds, we have this baby who is clearly sick and that doesn’t go away.”
Kelly Cervantes, CURE board member will host the weekly podcast, delivering interviews with her husband, best-selling author Kurt Eichenwald, patients, parents, medical professionals and others in the epilepsy community bringing the critical need for epilepsy research to the forefront while teaching empathy and inspiring hope.
“We believe it is vital to share the impact epilepsy has on families,” says Kelly Cervantes, “and to share resources and insights from clinicians, researchers and advocates as we seek a cure for epilepsy.” You can find the first three episodes of the Seizing Life podcast at www.SeizingLife.org:
The mission of Citizens United for Research in Epilepsy (CURE) is to find a cure for epilepsy, by promoting and funding patient-focused research. Since its inception in 1998, CURE has raised over $60 million to advance its goal of no seizures and no side effects. To date, CURE has awarded more than 220 cutting-edge research projects in 15 countries around the world. CURE is the leading nongovernmental agency fully committed to funding research in epilepsy.
Seizing Life, a weekly CURE podcast hosted by CURE Board Member Kelly Cervantes, brings you inspirational and helpful stories from those impacted by epilepsy. Kelly interviews patients, advocates, caregivers, and medical professionals to bring the critical need for epilepsy research to the forefront, while teaching empathy and inspiring hope.
A potential method of predicting who will get epilepsy following a brain infection, such as that brought on by malaria, has been discovered. This breakthrough is the result of work by two CURE grantees, Dr. Bruce Gluckman and Dr. Steven Schiff of Pennsylvania State University.
Individuals who contract cerebral malaria (malaria accompanied by a coma, typically spread by mosquitos) are at a substantially increased risk of developing epilepsy.1 Malaria is especially widespread in non-industrialized areas of the world and often affects children.2 Because malaria is so widespread, it may be the most significant cause of post-infection epilepsy in the world today. Currently, there are no methods to predict who will develop epilepsy, or any means of preventing epilepsy after such an infection.
This makes Dr. Gluckman and Dr. Schiff’s discovery so critical. Together with their team members Fatemeh Bahari and Dr. Paddy Sstentongo, they found a combination of brain and heart activity in mice that could accurately predict which animals would develop seizures and epilepsy after infection with malaria.3
Using their CURE grant, Drs. Gluckman and Schiff studied the connection between cerebral malaria and epilepsy by first developing a mouse “model” replicating malaria-induced epilepsy. In addition, they investigated possible ways to determine which mice would go on to develop epilepsy after infection.
Using the mice which developed epilepsy after infection with malaria, the research team measured two important variables often associated with epilepsy: the activity of the brain and heart. They found abnormal brain activity immediately followed by abnormal heart activity – but only in the animals which went on to develop epilepsy.
This discovery represents a possible biomarker for predicting epilepsy following infection with malaria. In other words, these may be measurable indicators to determine the infected individuals who will develop epilepsy. Furthermore, the abnormal brain and heart activity was detectable as early as 14 weeks before the first seizure, opening a potential window during which therapeutic interventions might be used to prevent epilepsy.
Drs. Gluckman and Schiff plan to continue this work, using these findings to develop treatment methods for people who contract cerebral malaria to prevent them from developing epilepsy. They are hopeful their discovery will lead to a means to eliminate not only post-malarial epilepsy, but also epilepsy caused by other types of brain injuries.
The new year always sparks renewed motivation in the fight against epilepsy, but 2019 also brings a new way to increase awareness and understanding: Seizing Life, a CURE podcast!
Released weekly, Seizing Life is hosted by CURE Board Member Kelly Cervantes. Episodes feature interviews with members of the epilepsy community on topics including creating individualized education plans, how raising special needs children can impact a marriage, and epilepsy genetics.
Seizing Life launches later this month. You can watch the trailer and read more about this exciting new podcast below.
Also in this update…
Raise Epilepsy Awareness and Funds for Research as a CURE Champion!
CURE Scholar Derek Vielhauer on How His Scholarship Is Helping Him Become an Agent of Change
Laura S. Lubbers, PhD
Seizing Life, a CURE Podcast, Launches This Month! Seizing Life, a weekly CURE podcast hosted by CURE Board Member Kelly Cervantes, brings you inspirational and helpful stories from those impacted by epilepsy. Kelly interviews patients, advocates, caregivers, and medical professionals to bring the critical need for epilepsy research to the forefront, while teaching empathy and inspiring hope.
Check out a sneak peek of Seizing Life:
The podcast launches later this month and will be available on iTunes, Google Play, and other major podcast platforms. You can follow Seizing Life on Facebook, Twitter, and Instagram.
Raise Epilepsy Awareness and Funds for Research as a CURE Champion! Use your unique talents to host a CURE Champion event or campaign! As a CURE Champion, you will bring fun, enthusiasm, and awareness to your community, while raising vital funds for groundbreaking research.
Getting started is easy…
Decide what your event or campaign will be. You can host a dance class, art exhibition, 5K run, bake sale, or online birthday fundraiser. Be creative!
Set up a fundraising page. Your page can be on our platform, Facebook, or your own website.
Tell CURE about your event. We’re here to help by promoting your event online and by providing you with promotional materials. Please reach out to us at events@CUREepilepsy.org or 312.255.1801.
Spread the word! Use social media, email, and word-of-mouth to let your community know about your event. Share why raising funds for epilepsy research is so critical and encourage people to join you as an attendee, donor, sponsor, or volunteer!
Have an idea, but aren’t sure how to get started? Our Development Team would love to hear it and help! Reach out to events@CUREepilepsy.org or 312.255.1801.
CURE Scholar Derek Vielhauer on How His Scholarship Is Helping Him Become an Agent of Change Each year, CURE is pleased to offer Education Enrichment Fund (EEF) scholarships, made possible by the generous support of Lundbeck, to those impacted by epilepsy, their families, and their caregivers.
In 2018, we awarded one of these $5,000 scholarships to Arizona State University (ASU) student Derek Vielhauer, who was diagnosed with epilepsy as an infant. He says epilepsy defined the first seventeen years of his life, but also gave him a passion for advocacy and research.
“With this generous scholarship, I have been able to continue working towards my dream of graduating with a Bachelor of Science and Engineering in biomedical engineering. In addition to researching methods to address neural deficits at ASU, I am collaborating with a neurosurgeon at Mayo Clinic and with an ASU neural engineer to develop innovative medical technology for patients suffering from neuro-diseases.
“I could not do this without the financial support the CURE EEF scholarship has provided me. This scholarship allows me to continue pushing forward through the rigorous engineering program without the financial worries which would exist otherwise.” – Derek Vielhauer
You could become one of our 2019 EEF scholars. We’re accepting applications until April 15, 2019. For details regarding eligibility requirements, please click here or contact CURE at scholarship@CUREepilepsy.org.
These one-time scholarships are awarded to those living with epilepsy or to family members and caregivers of those impacted by epilepsy. The scholarships support coursework aiming to advance personal knowledge in epilepsy research, health education, awareness, and/or advocacy.