2013 - 2018 Summary Report Our MISSION: To reduce seizures and improve quality of life for people with drug-resistant epilepsy. Our successes are the result of dedicated researchers, clinicians, institutions, community advisors and industry partners. On behalf of EpLink, we are pleased to share this summary report highlighting our accomplish- ments over the past 5 years. We are proud to be at the forefront of epilepsy research and leading the search for better treatments for the over 90,000 people in Ontario with epilepsy. Our successes are the result of dedicated researchers, clinicians, institutions, community advisors and industry partners. Our collaborators help us to move our research outside of academia and into the community, where its impact can truly be felt. Epilepsy does not live in hospital beds or university labs. It lives in homes, in communities, in schools, in those trying to live well with a disease that is still not fully understood. We are privileged to count some of the best and brightest minds in Ontario among our collabora- tors as we continue to strive for innovative treat- ments that reduce or eliminate seizures. However, epilepsy is not just a seizure disorder, and we are working to manage and reduce the impact of the co-existing conditions that many people with epilepsy face. In all of this, we are guided by our community partners, and particularly our Commu- nity Advisory Committee, as we strive to ensure that our research is relevant and reaches the people who need it most. As we look to the next phase, we would like to thank all of our supporters for your passion and dedication to epilepsy research. We look forward to expanding our network over the next 5 years, and building a truly collaborative research pro- gram that positively impacts the lives of people with epilepsy in Ontario, one discovery at a time. Jorge Burneo, MD, MSPH, FAAN, FAES Professor of Neurology and Epidemiology Jack Cowin Epilepsy Research Chair Co-Director, Epilepsy Program Department of Clinical Neurological Sciences Schulich School of Medicine, Western University Medical Director, EEG Laboratory, London Health Sciences Center Mary Pat McAndrews, PhD, C.Psych Practice Leader in Psychology, UHN (PM, TG, TW sites) Senior Scientist, Krembil Research Institute Chair, Trainees Affairs Committee, Krembil Research Institute Professor of Psychology, University of Toronto Director, Neuropsychology Clinic, Toronto Western Hospital McIntyre Burnham, PhD Professor Emeritus, Department of Pharmacology and Toxicology University of Toronto Director, University of Toronto Epilepsy Research Program Message from our Co-Directors Page 1 of 11 Issue 1, FALL 2018 Quarterly Newsletter Our VISION: A world without epilepsy. THE EPILEPSY RESEARCH PROGRAM OF THE ONTARIO BRAIN INSTITUTE
Transcript
2013 - 2018 Summary Report
Page 1 of 8
Our MISSION: To reduce seizures and improvequality of life for people with drug-resistant epilepsy.
Our successes are the result of dedicated researchers, clinicians, institutions, community advisors and industry partners.
On behalf of EpLink, we are pleased to share this summary report highlighting our accomplish-ments over the past 5 years. We are proud to be at the forefront of epilepsy research and leading the search for better treatments for the over 90,000 people in Ontario with epilepsy.
Our successes are the result of dedicated researchers, clinicians, institutions, community advisors and industry partners. Our collaborators help us to move our research outside of academia and into the community, where its impact can truly be felt. Epilepsy does not live in hospital beds or university labs. It lives in homes, in communities, in schools, in those trying to live well with a disease that is still not fully understood.
We are privileged to count some of the best and brightest minds in Ontario among our collabora-tors as we continue to strive for innovative treat-ments that reduce or eliminate seizures. However, epilepsy is not just a seizure disorder, and we are working to manage and reduce the impact of the co-existing conditions that many people with
epilepsy face. In all of this, we are guided by our community partners, and particularly our Commu-nity Advisory Committee, as we strive to ensure that our research is relevant and reaches the people who need it most.
As we look to the next phase, we would like to thank all of our supporters for your passion and dedication to epilepsy research. We look forward to expanding our network over the next 5 years, and building a truly collaborative research pro-gram that positively impacts the lives of people with epilepsy in Ontario, one discovery at a time.
Jorge Burneo, MD, MSPH, FAAN, FAESProfessor of Neurology and Epidemiology
Jack Cowin Epilepsy Research Chair
Co-Director, Epilepsy Program
Department of Clinical Neurological Sciences
Schulich School of Medicine, Western University
Medical Director, EEG Laboratory, London Health Sciences Center
Mary Pat McAndrews, PhD, C.PsychPractice Leader in Psychology, UHN (PM, TG, TW sites)
Senior Scientist, Krembil Research Institute
Chair, Trainees Affairs Committee, Krembil Research Institute
Professor of Psychology, University of Toronto
Director, Neuropsychology Clinic, Toronto Western Hospital
McIntyre Burnham, PhDProfessor Emeritus, Department of Pharmacology and Toxicology
University of Toronto
Director, University of Toronto Epilepsy Research Program
Message from our Co-Directors
Page 1 of 11
Issue 1, FALL 2018Quarterly Newsletter
Our VISION: A world without epilepsy.
THE EPILEPSY RESEARCH PROGRAM OF THE ONTARIO BRAIN INSTITUTE
Research Highl ights : 2013 - 2018
For a person living with drug-resistant epilepsy, life can present many challenges. Approximately one-third of the 90,000 people with epilepsy in Ontario will have seizures that cannot be controlled with medication. For these individuals, finding the right treatment may involve surgery, diet therapy or new kinds of drugs. EpLink supports research across the continuum, from basic science to clinical trials. Using basic science methods, we are discovering the genetic changes that can lead to the development of seizures. With this information, we have developed and tested models of rare epilepsies and can identify new targets for drug development.
Basic science also allows us to study patterns of brain activity to understand how seizure activity develops and spreads. As we move into hospital epilepsy monitoring units, we can use this knowledge to analyze and interpret brain recordings to learn more about a person’s seizures. For people who are having epilepsy surgery, measuring and observing their brain activity can help us to identify where seizures are starting, how far they spread, and how surgery may potentially impact critical functions such as language. Cutting-edge imaging techniques are also used to understand how the brain can reorganize itself in people with epilepsy, and to identify areas of seizure activity as accurately as possible before surgery. New imaging techniques can also identify brain networks responsible for language and memory and how these may be impacted by seizures and surgery.
Outside of the lab, we are focused on prevention and screening, and have identified factors that can increase the risk of developing seizures, such as low birth weight and tuberous sclerosis. We have learned about which individuals may have an increased risk of sudden death in epilepsy, a rare but devastating occurrence, and how much information families want to receive about these risks.
EpLink is even working in the realm of what was once considered science fiction, where wearable technology has enabled headsets that can warn of upcoming seizures, and a "smart" implantable computer chip can detect and stop seizures in the brain before they start.
Along with innovative treatments, we are also deeply invested in outcomes, such as how the ketogenic diet can reduce health care costs, how epilepsy affects school performance and the long-term effects on
quality of life after childhood epilepsy surgery.
EpLink is focused on epilepsy care throughout the lifespan, from screening infants at risk of developing infantile spasms to prevent the development of seizures, to studying how children with epilepsy manage the day-to-day demands of independent living, to uncovering the links between epilepsy and other genetic syndromes. Recognizing the need for broader education and awareness, a community-based referral program was developed that offers information, support and training tools to those
navigating the different aspects of an epilepsy diagnosis. Finally, EpLink researchers helped to establish a comprehensive series of guidelines that aim to improve the quality and consistency of epilepsy treatment across the province and empower people with epilepsy to make informed decisions about their care.
EpLink’s work over the past 5 years has helped to transform the field of epilepsy research. In the next phase, we will continue to build on our successes, bringing high quality science and innovation to Ontario that can truly impact the lives of people with epilepsy.
Providing Hope for People with Drug-Resistant Epilepsy
• The slow initiation of the ketogenic diet (KD) was found to be safe and allowed many patients to achieve good seizure control, including seizure freedom, at low ratios of fats to carbohydrates. Overall, success with the KD was better in younger patients.
• The reduction in hospital visits in children on the KD resulted in significant cost savings to the health care system.
• OHIP now covers KetoCal, a nutraceutical formula in a 4:1 ratio (fat: carbohydrate and protein).
◦ This achievement is promising for EpLink’s industry partner Ketogen, a company developing an alternative product to KetoCal.
• Ketogen’s novel therapeutic, in the form of a pill, may provide reduced dose/drug-related side effects in patients with epilepsy.
GENETICS AND EPIGENETICS• The EpLink Genetics Project team has collected and entered data from patients with epileptic encephalopathies into Brain-CODE.
◦ This data is being analyzed for genetic causes and modifiers of controlled and uncontrolled epilepsy.
• Through whole genome sequencing, research has identified one gene associated with SUDEP and found that adults who have a certain type of epilepsy (from a mutation in the PCDH19 gene) are at
increased risk of schizophrenia.
• A mutation believed to cause drug-resistant epilepsy has been engineered into mouse embryonic stem cells.
◦ Using CRISPR/Cas9-mediated gene editing, the mutation was converted back to the normal gene sequence. This editing strategy is being investigated in vivo.
• After participating in either the UPLIFT or EpINFO educational programs, people with epilepsy showed improvements in depression and quality of life. These improvements, however, were not sustained six months later.
• A computer-based training tool, called CogMed, may improve working memory of children with epilepsy.
• In a series of studies, it was found that patients who had epilepsy surgery in childhood achieved seizure freedom faster and used fewer anti-seizure medications at follow-up (4-11 years later) compared to patients who did not have epilepsy surgery during childhood.
◦ These studies documented the aspects of cognition that remain stable over time or change as a function of seizure status.
QUALITY OF LIFE
• A large pediatric population-based study of SUDEP in children reported that sudden unexpected death in epilepsy (SUDEP) is as common in children as in adults.
◦ This is an important consideration when counselling pediatric patients and families.
• Reduced brain activity after a seizure, called Postictal-Generalized EEG Suppression, may be a way to identify patients at risk for SUDEP.
• Clinicians have begun screening infants at risk for West’s syndrome, a severe form of epilepsy, by conducting regular EEGs and checking for hypsarrythmia, an EEG pattern associated with infantile spasms.
◦ The team identified four cases of infants with hypsarrythmia, and have been actively managing these cases with drug therapy (i.e. vigabatrin), with the goal of eliminating hypsarrythmia by the 12-month EEG follow-up.
EPIDEMIOLOGY AND DIAGNOSIS
DIET THERAPY
Page 4 of 11
Research Highl ights : 2013 - 2018
• New models to predict memory and language outcome after surgery have been developed.
◦ These new models are being disseminated widely (i.e. in presentations, papers, etc.) to influence clinical practice.
• Using high-resolution MRI techniques to identify lesions in the brain not seen on conventional imaging, will allow better identification of potential epileptogenic regions in the brain, improving the outcomes of patients after surgery.
• Researchers are in the process of prototyping a novel technology for minimizing head motion artifacts in magnetoencephalography (MEG), and improved MEG facilities are now available at SickKids and Toronto Western Hospital.
◦ This work has the potential to reduce or even eliminate the need for sedating young patients during standard MEG, increase the accuracy of preoperative imaging, and may pave the way for better standard of care.
• Researchers at Western University and King’s College London have submitted a (British) EPSRC Centre-to Centre grant to evaluate transcranial magnetic (TMR) imaging in the diagnosis of epilepsy and planning surgical procedures.
◦ The grant focused on the precise imaging of stereoelectroencephalography electrodes relative to anatomical targets in the brain.
IMAGING AND SEIZURE SURGERY
• EpLink partnered with Avertus Inc., a company that has developed a wireless headset to detect the onset of seizures and provide seizure warnings to people with epilepsy whenever needed.
◦ The headset is now being sold to researchers and will soon be approved for testing on patients with epilepsy.
• Researchers have developed a method to anticipate seizures and to stop seizure generation using intracerebral electrical brain stimulation.
◦ The team has developed a novel computer chip (Neural Interface Processor – aka NURIP) that can be surgically placed within brains of people with epilepsy to deliver brain stimulation when a seizure is about to start.
◦ This method has been effective in stopping seizures in animals, and now, human studies have begun with hopes that it will have the same effect.
BRAIN MONITORING AND MODULATION
• Animal models show that cannabidiol (CBD) – the extract in medical marijuana that doesn’t make you high – has been shown to stop seizures in animal models.
◦ Along with our industrial partner, EpLink is close to recruiting patients for a clinical trial examining the effects of CBD in adults with drug-resistant epilepsy.
• An entirely new type of seizure medication is being developed from animal studies on Rett Syndrome, a genetic disorder that may result in both intellectual disability and seizures.
◦ “Rett-like” mice have an overly active protein called histone deacetylase 6 (HDAC6).
◦ The drugs work by inhibiting HDAC6 activity, thereby stopping seizures in animal epilepsy models (i.e. in wild-type mice).
◦ Researchers are working with EpLink’s industrial partners to test the toxicity of the drugs for chronic use. If the drugs are well-tolerated, then the group can begin submitting applications to move the drugs towards clinical use.
DRUG THERAPY
Community Advisory Committee
Provide guidance on research priorities; collaborate on knowledge translation and dissemination; assist with study development; link to broader epilepsy community Support provided by the
Ontario Brain Institute; collaborate with policy makers; health care advocacy
Industry Partners
Community Epilepsy AgenciesSupport and collaborate on EpLink events and knowledge translation initiatives; disseminate research findings
Helping bring discoveries from bench to bedside
Government of Ontario
Page 5 of 11
EpLink : A Truly Col laborat ive Program
Personwith
DRUG-RESISTANTEPILEPSY
Screening &prevention
CommonData
Elements
Education&
awareness
Co-existing
conditions
SUDEP
EEG andNeuroimaging
Preclinical(animalstudies)
ClinicalTrials
EPILEPSYSURGERY
DRUGDEVELOPMENT
GENETICS
Guidelines
DIETTHERAPY
BRAINSTIMULATION
QUALITYOF LIFE
Ontario Epilepsy Guidelines
Development• During Phase 2, EpLink created multiple summary versions of the Provincial Guidelines for Epilepsy Care developed by the Epilepsy Implementation Task Force. These recommendations were developed to help improve the quality and consistency of clinical care for epilepsy in Ontario.
• A major “take-home” message in the Guidelines is that people with drug-resistant epilepsy must be referred to specialty centres that can offer other treatment options, including diet therapy and surgery.
Promotion• The guidelines website and YouTube page were launched on March 1, 2018.
• Copies of the guidelines summaries were distributed to all Community Epilepsy Agencies in Ontario.
• Clinician versions of the guidelines were sent to all neurologists in Ontario, along with hundreds of family doctors and nurse practitioners.
• EpLink promoted the guidelines via several public talks and through social media channels (i.e. Twitter, Facebook).
• March 2018 article in Toronto Star insert, published by MediaPlanet, and article on personalhealthnews.ca
• Raw Talk Podcast, episode #20, featuring Mac Burnham, July 2017
• Press releases (Katie’s Run to fund Genetics Project, Epilepsy surgery success story)
• IMS Magazine article, by Jabir Mohamed, March 2015
• CTV news article, Sept 2015
• Vancouver Sun article, Sept 2015
Media Presence
Public Education Events
Fundraising Events
2017 Joint event with CAN-BIND called “How to Cope? A Discussion for People Living with Epilepsy and Depression/Anxiety”
2016-18 Purple Day epilepsy awareness days (booths at Brookfield Place and U of T Medical Sciences Building)
2016 “Open Forum: Mortality in Epilepsy” event
2015 “Medical Marijuana & Seizure Management Forum” held in partnership with Epilepsy Toronto
2017-18 Katie’s Run for Epilepsy - assisted with event coordination and soliciting donations and sponsors
2016 “Dueling Pianos for Epilepsy” event, with joint fundraising for EpLink and Epilepsy Southwestern Ontario
2016 James-Bond themed joint fundraising event/gala, “Shaken Not Stirred”, raising funds for both EpLink and Epilepsy Ontario
2015 “All-in for Epilepsy” silent auction and poker night
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