Dravet Syndrome is a severe and extremely rare but catastrophic neurological disorder affecting young children (approximately 1 in 19,000 people). Every day 3 or 4 children are diagnosed with Dravet syndrome worldwide, with symptoms including epilepsy, autism, movement disorders, and sleep disturbances. To date, the majority of therapies are ineffective or poorly tolerated. Sodium channel drugs, which are some of the most commonly prescribed and effective antiepileptic drugs may even worsen Dravet syndrome.
Dr Lignani said: “This MRC New Investigator Research Grant was only possible due to my ERUK Fellowship Award. Support from Epilepsy Research UK has enabled me not only to apply for this grant, but to collaborate with a team in Italy to learn about key advanced molecular genetic techniques that can be implemented in our lab at the Institute of Neurology. This further research grant is recognition of the high standard of ERUK-funded research.”
He continued “This research will be useful not only to understand if a permanent general treatment for Dravet syndrome is achievable, but will also give insight into the potential of the techniques to cure other neurological conditions caused by similar mutations in different genes.”
Dr Lignani’s ERUK Fellowship officially began in 2018 but is already showing promising results. His team’s work thus far has focused on developing and testing their gene therapy tools, and they have found that this tool is able to subdue neurons during epileptic activity. The following stages of the fellowship will involve trialing these tools in models of acquired intractable epilepsy.
Carolyn Fahm is a retired biochemist who specialised in immunochemistry and trace element analysis. Carolyn has lived with epilepsy since her teenage years. In this piece, she shares her thoughts about the importance of the research that ERUK is funding for 2019.
How epilepsy research impacts patients’ quality of life
The newly funded ERUK research grants for the current year have the potential to be life changing in very fundamental ways.
Currently, testing to find the epileptogenic locus requires days of hospitalisation and time off work. For children, the lengthy time confined by the many electrodes may be more than they can tolerate. The new wearable electrode cap, which Dr Vivekananda’s project will be using, will be revolutionary in being able to continue to monitor patients as they go about their days in their normal settings. Another project with life saving potential is investigating the prelude of SUDEP. Currently the first indication of SUDEP is the patient’s death. To be able to predict and then treat this is something that will reassure those living with epilepsy and give peace of mind to them and their loved ones.
I received an epilepsy diagnosis many years ago based on an eye witness report and confirmatory testing, both the fruits of epilepsy research. Basic research into neural activity during seizure produced the electroencephalogram (EEG).
Anti-seizure drug therapy was available in the form of Dilantin, the drug of first choice, Phenobarbital, a drug of long standing that had been trialled for its seizure calming effects by researchers, and then a drug new at that time, Tegretol. The latter drug turned out to be the only one of the three that gave me seizure relief without allergic side effects as the other two had done. Since then I have greatly benefitted from the introduction of a new drug with a new method of action and far fewer side effect, Vimpat.
For me, as for many others, drug therapy has made it possible to live mostly seizure free, because I have had breakthrough seizures intermittently, but not without side effects. From nausea and dizziness for my first month on Tegretol to the sedating effects and hyponatremia (low sodium content in the blood) of Trileptal, side effects have gone hand in hand with seizure relief for me and many others. For this reason, the grant awardees’ quest for a drug specific only to seizure-inducing neurons and not the rest of the brain would be transformative to the ability of epilepsy patients to live fuller, richer lives.
Epilepsy Research UK is unique in funding researchers at all levels of their careers, from the young scientists doing doctoral thesis research through mid-career researchers up to researchers of many years standing at the peak of their careers in neuroscience. Innovation and breakthroughs may come from any point in a researcher’s career, something that is clear from looking at the backgrounds of the grant recipients. ERUK is investing in the future lives of people living with epilepsy. With one per cent of us living with epilepsy, the payoff from these projects will impact thousands; all the more reason to make the investments now to better serve the patients of the future as well as those of us who are currently benefitting from the fruits of past research.
You can read all about the 2019 grant awards here.
We are delighted to share with you our new-look Focus Newsletter, which brings you news of our grant awards for 2019/20. Please select the fullscreen option to read in the display below or click on the top left of the image to download your copy.
Inside you will find information about the projects selected and an overview of the process our Scientific Advisory Committee undertakes to ensure only the best quality research is funded. There are also fundraising highlights and much more.
To be the first to receive all future newsletters from Epilepsy Research UK, please join our mailing list here.
This week is Carers Week: an occasion to celebrate the valuable role that carers play in the lives of people with long term health conditions and disabilities. Clare Kassa is Chief Executive of Sibs, a charity supporting the brothers and sisters of people with disabilities. This week Sibs are highlighting the important role sibling carers play.
Sibling carers play a vital role in the lives of their brothers and sisters, often providing lifelong care, support and advocacy. It is a role often little recognised or understood. Sibling carers contact us every week looking for support, information and the opportunity to link with others who understand their sibling journey. Jayne, aged 61, cares for her brother Frazer, who lives with epilepsy and a learning disability. This is her story:
“My brother is 6 years younger than me, so I have always looked out for him. I remember as a teenager being left in charge of him whilst my parents went to a school event, and my brother had a tonic clonic seizure. He had come down the stairs and said he didn’t feel well and he needed to be with someone. I was really scared and tried to remember what my Mum had told me to do if Frazer had a seizure. I remember speaking to him calmly, got him sitting on the sofa next to me and hugged him. The seizure started and went on for about five minutes and he fell to the floor. I stayed next to him on the floor to try to stop him hurting himself. In those days there were no mobile phones, I just had to wait for my parents to come back. I just talked to him and reassured him and covered him with a blanket. Afterwards he was exhausted and disorientated. I have never forgotten that early experience.
“As Frazer became a teenager, we went through a lot in trying to get his epilepsy controlled better and his medication was changed. As a family, we had to live around his needs, excitement could trigger a seizure, so we had to downplay holidays and special times like birthdays and Christmas, as it would mean celebrations would be cancelled for all of us siblings.
“As an adult sibling carer to Frazer, his health is a constant worry to me. I worry that when paid carers look after him, that they fully understand how traumatic an experience a seizure can be for him. I worry about him falling, as now he is in his 50s and his mobility is poorer. I worry about him overnight and him getting enough rest. He has difficulties sleeping at times and we know that sleep problems can be a trigger for his epilepsy. Whenever we take him swimming, we make sure we tell the lifeguard about Frazer’s epilepsy, so that they are aware, as the light reflecting on the pool can also be a trigger for him. At the moment, his medication seems to be controlling things well, but we review his treatment regularly with his doctors.
“I feel like I have been on an emotional roller coaster with Frazer all of my life. I often feel he has been given a raw deal, but he is happy and enjoys his life and never complains. I love him and want the best for him, we have a lot of fun together. We have a shared history, I know all the things about him, that make him happy or sad and I will fight for his needs always.”
Young Sibs is the youth arm of Sibs charity, supporting child carers. You can find their spotlight on young sibling issues here.
Epilepsy Research UK is delighted to announce that one of our funded researchers, Dr Gashirai Mbizvo, has been awarded the 2019 Charles Symonds Prize for Best Platform Presentation by a Junior Neurologist at the Association of British Neurologists Annual Meeting in Edinburgh.
The Association of British Neurologists is the membership body for neurologists in the UK, and aims to promote excellent standards of care and champion high-quality education and world-class research in neurology. Their annual meeting is an opportunity for leading neurologists in the UK to present their ground-breaking research to their peers. The ABN membership is not just limited to epileptologists, but includes clinicians from all neurology subspecialties such as movement disorders, stroke, motorneurone disease, and brain injury.
Remarkably, this is not the first national award Dr Mbizvo has won for this project – he has previously won awards at the 2018 International League Against Epilepsy (ILAE) British Conference, and at the 2017 Scottish Association of Neurological Sciences Conference. In March this year Dr Mbizvo and Dr Duncan also visited Scottish Parliament to speak about their important work.
Huge congratulations Dr Mbizvo, Dr Duncan, and the rest of the research team, from all of us at Epilepsy Research UK!
Last night at the House of Commons we were pleased to stand alongside a number of charities who have all agreed to work together to improve outcomes for people with neurodevelopmental conditions.
The Embracing Complexity Coalition, lead by the team at Autistica, has released a report summarising the results of a survey of people living with Neurodevelopmental conditions to stimulate further discussion and debate. The charities have aligned due to the growing recognition that neurodevelopmental conditions often share symptoms and most people affected have more than one of these conditions – and often many.
The charities believe that a more integrated approach is required and have taken the first step by forming a coalition.
Epilepsy Research UK has long identified this as a priority area and in March of this year we brought together 50 of the world’s leading experts in epilepsy and neurodevelopmental disorders research for a two day workshop.
The 12th International Expert Workshop was comprised of six sessions, each exploring a different aspect of epilepsy and neurodevelopmental disorders. The session themes ranged from epileptic encephalopathy, genetic epilepsies, behaviour and development, to molecular therapeutic strategies. Each session was followed by a chaired discussion to help identify and prioritise future research directions and forge collaborations. To read more about our 12th International Expert Workshop, click here.
We are looking forward to being an active member of the coalition and will be calling for further investment into this vital area of work.
On 14th and 15th March 2019, 50 world leading experts in epilepsy and neurodevelopmental disorder research were brought together by ERUK for our 12th International Expert Workshop at St Anne’s College, Oxford. Our International Expert Workshop first began in 1993, and since then has been a recurring biennial event.
This workshop was chaired by Professor Sameer Zuberi from the Royal Hospital for Sick Children in Glasgow, Professor Stuart Cobb from the University of Edinburgh, and Professor Oscar Marin from King’s College London, who are renowned leaders in both basic science and clinical aspects of epilepsy and neurodevelopmental disorders. They said “Epilepsies with onset in childhood are associated with significant comorbidities affecting learning, motor control, cognition, and behaviour. The epileptic seizure may be the presenting symptom and most dramatic expression of a brain disease, but it is the impact of the underlying condition on learning, behaviour, and participation in society which results in the most disabling consequences for the child and family. Anti-seizure medications are designed to control events but disappointingly have little or no impact on the neurodevelopmental comorbidities of epilepsy.”
The workshop attendees were clinicians and scientists working at the frontiers of neuroscience and epilepsy research, bringing a varied range of interests and expertise, and representing all the key research themes linking neurodevelopment and epilepsy. Delegates came from a total of 36 institutions, spanning 11 countries across 3 continents. Speakers included Professor Ingrid Scheffer from the University of Melbourne, Professor Jack Parent from the University of Michigan, Professor Dennis Lal from the Cleveland Clinic and Broad Institute of Harvard and M.I.T, Professor Scott Baraban for the University of California San Francisco, as well as ERUK’s President, Professor Helen Cross from Great Ormond Street Hospital. ERUK also invited a number of leading experts in the field to take part in the discussions following each session and at the end of each day.
The Expert Workshop comprised of six sessions, each exploring a different aspect of epilepsy and neurodevelopmental disorders. The session themes ranged from epileptic encephalopathy, genetic epilepsies, behaviour and development, to molecular therapeutic strategies. Each session was followed by a chaired discussion to help identify and prioritise future research directions and forge collaborations. What’s remarkable about the expert workshop is that it is very small, compared to many other scientific conferences. But we have found that it is its very size that makes it so effective in facilitating discussion, collaboration and priority setting.
When welcoming the delegates to the workshop, Professor Bruno Frenguelli, Chair of ERUK’s Scientific Advisory Committee said: “The birth of a child is a momentous and joyous occassion in the lives of the parents. However, for all too many parents, this joy is curtailed by the realisation that there is something wrong with their child. This earth-shattering revelation often first manifests itself as the appearance of epileptic seizures, for which, unfortunately, there are limited treatment options. The Workshop is thus an opportunity for the expert community to consider the basis of neurodevelopmental epilepsy, to discuss the most appropriate models and diagnostic approaches, and to explore the potential treatment options for afflicted children.”
Highlights included Professor Stephanie Schorge’s talk on recent advances in gene therapy (which touched on work by ERUK Fellow Dr Gabriele Lignani), Dr Richard Rosch’s talk on zebrafish models of epilepsy, Professor Scott Baraban’s talk on interneuron-based cell therapy for intractable epilepsies, and Professor Michael Johnson’s talk on computer-based models of epilepsy. Professor Johnson highlighted the complexity of the workshop theme: “There are currently over 1000 epilepsy-related genes and 8000 known drugs, meaning there are a minimum of 8 million possible combinations of genes and drugs to be studied. This lends itself to computational solutions to assessing candidates for drug repurposing.” A talk from Professor Dennis Lal on rare genetic epilepsies and neurodevelopment drew gasps of amazement from the audience, as he debuted a brand new online tool to help interpret genetic variants of epilepsy.
All workshop attendees agreed that the event had influenced their future research or clinical practice, and that they had all left with significant new learnings with regard to research into epilepsy and neurodevelopmental disorders. We look forward to seeing the doubtless scientific breakthroughs from the countless new collaborations that the workshop has forged, over the coming months and years.
Workshop chair Professor Sameer Zuberi said: “This meeting would not have been possible without the willingness of busy people to share their ideas, expose them to critique, and to travel a long way to do this. We thank all members of this exceptional international faculty – presenters and discussants – for agreeing to meet in Oxford. We know that colleagues are prepared to do this for many reasons; their passion for science and intellectual discourse included but primarily because they respect and value the work of colleagues. As scientists we know that each increment in knowledge, every marginal gain, when added together can make big differences to the lives of people with epilepsy.”
A summary of the topics discussed at the workshop is due to be published in a special issue of the European Journal of Paediatric Neurology. This special issue of the journal will also set out the future research priorities for epilepsy and neurodevelopmental disorders. Several of the experts who attended the workshop will be contributing articles to this special issue, which we hope to share with you on our website in due course.
We would like to extend our sincere thanks to all of the delegates who contributed to making this year’s workshop such a success, and to each of our supporters, whose tireless fundraising helped make this workshop possible.
You can access the workshop programme by clicking on the image below:
On Monday 20th May, to launch National Epilepsy Week, we announced an investment of over £1 million across ten potentially life changing and life saving epilepsy research projects in the UK. This investment brings the total amount the charity invested in scientific and clinical research to over £10 million.
Speaking at the event, Professor Matthew Walker, our Chair of Trustees, said welcomed supporters and researchers to the event and introduced ERUK’s new strategy. He said “It is only through research that we will understand more about what causes epilepsy, how to best treat it, how to reduce the side effects of medication, how to treat those with intractable epilepsy and ultimately how to save lives.” Professor Walker spoke about the recent work the charity has been doing, and the development of our new strategy with our Chief Executive Maxine Smeaton.
Professor Bruno Frenguelli, Professor of Neuroscience at the University of Warwick and Chair of ERUK’s Scientific Advisory Committee took to the stage next to announce the newly funded research projects. Prof Frenguelli spoke about how each application went through a rigorous multi-stage application process, involving scrutiny by national and international epilepsy specialists before the final decision was made by the Scientific Advisory Committee. The ten newly funded research projects range in value from £25,000 to £250,000, and involve over 40 researchers across 28 institutions spanning 8 countries.
Each of our newly-awarded researchers made a short speech about their work and the potential impact this research could have for people with epilepsy in the future. For a number of the researchers who are at an early stage of their careers this funding will be transformative in enabling them to become future leaders in epilepsy research. This is especially the case for Dr Vincent Magloire, who is ERUK’s 2019 Fellowship Award holder. His research aims to find a new therapeutic target that can stop seizures in their tracks.
It is estimated that 21 people die every week in the UK as a result of epilepsy, and two of this years’ funded projects will aim to reduce epilepsy-related deaths by investigating the mechanisms underlying sudden unexpected death in epilepsy (SUDEP). In fact, these newly funded projects bring the total ERUK has invested in research into epilepsy-related deaths to over £1million since the organisation began.
You can read about each of the 2019 funded grants by clicking on the links below.
A huge highlight of the evening was our wonderful Donor Support Manager, Shona, receiving the Above & Beyond Award in recognition of 20 years of selfless commitment and dedication to Epilepsy Research UK. Long-standing ERUK supporter John Bettelley provided some words, he said “Shona has an encyclopaedic knowledge not only of all the research that goes on, but also the people involved throughout the country for 20 years or more. Shona has always been there for us and we know that will go for very many other people too.”
Our Chief Executive Maxine Smeaton was up next to unveil ERUK’s new strategy to our supporters. Maxine said “Now we will take our strategy from ambition to action.” The key elements of this implementation will be clear positioning of the charity, collaboration, and shared vision.
Regarding the newly funded research projects, Maxine said: “Research into the prevention, and treatment of epilepsy, as well as research into epilepsy-related deaths continues to be critically underfunded. As patients and their families search for new treatments, we hope that this investment in potentially life changing and life saving research into epilepsy will give them hope for the future.”
Maxine then shared a taster of ERUK’s refreshed brand, before leaving the audience with a video of our supporters’ and researchers’ hopes for the future of research into epilepsy. Watch the video by clicking on the below image:
We would like to thank all of our supporters and researchers for being part of this incredible evening.
Epilepsy Research UK’s 2019 Funded Research Grants:
Lead investigator: Dr Hanna Kovshoff, University of Southampton
Co-investigators: Dr Anna Moore, Southampton Children’s Hospital, Prof Sarah Parsons, University of Southampton, Dr Andrea Whitney, Southampton Children’s Hospital, Dr Charlotte Mead Southampton Children’s Hospital
Pilot grant: £30,000, 2 years
“We want to develop an understanding of child experiences of the epilepsy surgery pathway that takes into account their siblings, parents, peers, and schools. Given that schools are places where children and young people spend the majority of their time, educational experiences and related support are important, but often neglected considerations in the context of medical research.” Dr Hanna Kovshoff, University of Southampton
Background: Refractory epilepsy in children has serious implications for cognitive development, educational attainment, psychological well-being and quality of life. Surgery can help control seizures in childhood epilepsy if treatment with medication has been unsuccessful. However, for a number of different reasons, families can wait for a long time for decisions regarding surgery, and a proportion of children on this wait list are turned down. Very little is known about how these families feel about waiting for a decision, surgery, and their hopes and fears.
The Study: Dr Kovshoff and colleagues want to hear directly from children, their parents, and siblings about their experiences of the epilepsy surgery pathway and they will use different methods to approach this in a way that is sensitive to the children’s needs and the families’ circumstances. This pathway can be challenging for families due to the length of time awaiting a decision regarding surgery eligibility (12-24 months), numerous medical investigations, appointments, and the subsequent impact for children and families on school, friendships, work, and family life. The research will involve 15-20 children with epilepsy, at least one parent/carer per child and where appropriate, one sibling living in the same household (45-60 people).
Significance: Understanding patient and family experiences is vital to ensure that health and education services can provide appropriate support for patients and their families through this process. As increasing numbers of children are considered for epilepsy surgery, this pilot project will provide essential information aimed at improving services and support for children, parents and siblings. Uniquely, this study will also report on the psychosocial outcomes and experiences for children/families when they are not accepted for surgery. The results will inform service provision and be made available in the short-term through leaflets for children and families, and professionals in health and education.
Scientific Title: Predicting which brain region to treat: Multimodal Ictogenic Network Mapping (MINM)
Lead investigator: Dr Diana Cash, King’s College London
Co-investigators: Dr Michel Mesquita, KCL, Dr Marc Goodfellow, University of Exeter, Dr Laura Mantoan, KCL
Collaborator: Prof Mark Richardson, KCL
Pilot grant: £29,903, 12 months
“Our vision is to establish a translational platform to develop, test and optimise non-invasive multimodal mapping of seizure-generating networks in the brain, and to develop minimally-destructive techniques to disrupt them.” Dr Diana Cash, King’s College London
Resective brain surgery for focal epilepsy can be successful, but a significant number of patients do not become seizure free. Recent innovations in dynamic computational modelling have shown promise in mapping brain networks responsible for seizure generation (ictogenicity) and in predicting the outcome of specific resection strategies. It is highly challenging to translate this technique into prospective clinical use, because the model-predicted optimal resection may be substantially different from that predicted by conventional approaches.
In this pilot study, the researchers will test the feasibility of detecting epileptogenic networks using clinically-relevant functional neuroimaging, EEG and computer modelling techniques, in an animal model of epilepsy. Simultaneous specialised MRI and EEG scanning will be conducted prior to developing epilepsy, and then at regular intervals afterwards, in order to map the dynamic evolution of epileptogenic networks. The research team will then use this data to develop predictive modelling exploiting diverse information at different spatial scales and to determine the brain areas for surgical treatment – the ictogenic foci. The later steps will involve genetically modifying neurons in these brain areas to make them sensitive to light (optogenetics). This will briefly silence these model-predicted brain areas, in an attempt to validate the methodology before similar techniques can be applied to people with epilepsy.
This work will enable the researchers to properly test the efficacy of their proposed ictogenic network mapping for brain resection, using clinically relevant methods and endpoints, in an animal model. In future work, they will test these predictions in people with epilepsy. A successful outcome may be in clinical use in 5-10 years.