Research Report 2017

Funding Research, Transforming Lives Research Report 2017

Contents Forewords

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About Epilepsy Research UK

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About epilepsy

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Why we do research

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Current funding

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Research impact

8

Research recently completed

10

Shaping the future

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Grants awarded in 2017

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Grant funding process

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Thank you

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Forewords

Dr Graeme Sills, Chair of Trustees

Professor Mark Richardson, Chair of Scientific Advisory Committee

I am delighted to introduce the 2017 Epilepsy Research UK impact report. The research projects featured in this report, together with the summary details of new projects funded this year, illustrate the breadth of the research that we are currently funding across many important aspects of epilepsy. Since 2007 we have awarded almost £8 million in research grants and we are now aiming higher. Over the next few years, Epilepsy Research UK plans to increase the amount of money it makes available to research, but for that, we need our supporters’ help. The vast majority of funds that we raise for research come from the kindness and efforts of individuals. From people who leave us gifts in their wills, to people who organise walks, bake cakes, run marathons and dig into their piggybanks. This is the reason why we go to great lengths to ensure that we only fund the very highest quality epilepsy research at some of the world’s foremost academic institutions. The research that we do fund has and will continue to have a very real and positive impact on the lives of people with epilepsy.

Once again, in 2017, our Scientific Advisory Committee had a difficult job choosing from the many excellent applications for funding that were received. This year 28 project grants, 12 fellowships and 12 pilot grant applications were submitted. Fifteen projects, 5 fellowships and 7 pilot grants were shortlisted. One fellowship application was withdrawn from the grant round after it was shortlisted. The number and breadth of the grant applications received is encouraging, as they reflect an increasingly active and vibrant epilepsy research community in the UK. However; more still needs to be done to increase funding into epilepsy research, and it is important that we encourage talented researchers to enter and remain in the field. As Chair of the Scientific Advisory Committee, I am proud of the research that Epilepsy Research UK supports. It is of excellent quality and it will make a real difference to people with epilepsy now and in the future.

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About Epilepsy Research UK Epilepsy Research UK supports and promotes basic and clinical scientific research into the causes, treatments and prevention of epilepsy. The only national charity in the UK that is exclusively dedicated to funding independent research into this condition, Epilepsy Research UK was formed following the merger of the Epilepsy Research Foundation and the Fund for Epilepsy, in April 2007.

Epilepsy Research UK supports the work of scientists and clinicians throughout the UK, who are investigating all aspects of epilepsy in both adults and children. Our funded research projects focus on what causes epilepsy, who is at risk of developing it, what goes on in the brain during a seizure, and safer drugs and better surgical techniques to treat it.

Our annual research spending is about £700,000 – raised almost wholly through donations from the public – and we fund 4-9 new research projects each year.

Our funds support individual students and scientists based in university departments, medical schools and hospitals across the country. They also allow academic institutions to invest in much-needed equipment.

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In addition, Epilepsy Research UK arranges technical workshops and scientific meetings to encourage collaboration between researchers. We also work closely with other epilepsy charities to ensure that epilepsy is recognised in government health and social care policy.

Developments in drug therapy and medical scanning, along with major breakthroughs in the study of the human genome, mean that great progress has been made in understanding the causes of epilepsy in recent years. These are exciting times in epilepsy research and Epilepsy Research UK is proud to be supporting some of the key researchers in the UK, who are pushing forward our knowledge of epilepsy. Even greater advances will be made in the coming years and the research that we fund will be at the forefront of developments to control, and perhaps even cure, epilepsy.

Epilepsy is one of the most common neurological conditions.

32,000

Over 600,000 people in the UK have a diagnosis of epilepsy - 1 in every 103 people.

people in the UK are newly diagnosed with epilepsy each year – that’s about 87 people every day.

600,000

1,100 Every year 1,100 people die as a result of epilepsy-related causes.

60%

Epilepsy can take many forms, from a momentary blank spell to a dramatic major convulsion.

Epilepsy can be caused by a stroke, a head injury or an inherent genetic defect, but in over 60% of cases there is no known cause.

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Why we do research We fund research because currently 30% of people with epilepsy don’t respond to existing treatments, and many that do suffer unpleasant side effects.

Each year our Scientific Advisory Committee selects projects that we believe could make a real difference to the lives of people living with epilepsy.

Neuroscientists are now making discoveries and devising treatments that would be considered unthinkable only a few years ago. But we need to ensure that they are focusing on epilepsy as well as on other conditions. We need epilepsy specialists who dedicate their careers to investigating epilepsy, build up their expertise and train the researchers of the future.

More research into epilepsy is urgently needed, because we need to know more about: • what happens in the brain to produce a seizure • how to diagnose epilepsy earlier and more accurately • why some people are more likely to have seizures than others • which medications might work to control seizures better, and with fewer side effects • how to perform new surgical procedures that could control epilepsy

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• the genetic links of epilepsy • how to treat people whose epilepsy does not respond to medication, but who are not eligible for surgery • how to prevent sudden unexpected death in epilepsy (SUDEP) • the risks of antiepileptic drug exposure to unborn babies At Epilepsy Research UK, we fund studies into all these different aspects of epilepsy.

Our researchers are right at the cuttingedge of neurology, investigating the workings of the brain, how seizures happen and how to prevent them.

Since 2007 we have allocated almost £8 million in grant awards.

Some of that research has helped us: • improve epilepsy surgery for both adults and children • know more about risks of taking epilepsy medication in pregnancy • trial drugs to treat memory problems in people with temporal lobe epilepsy • improve surgery for focal epilepsy • discover that immunotherapy is an effective treatment for certain types of seizure Many of our grants support new pilots, giving researchers the opportunity to test out new ideas. This gives them the start-up they need, so that, hopefully, they can secure a larger grant from another funder.

Current funding

We are currently funding 31 projects at institutes around the country, with researchers investigating new methods of diagnosing and treating epilepsy, studying ways to prevent SUDEP, exploring ways to improve surgical outcomes and developing ways to improve the quality of life for people with epilepsy.

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1 Glasgow

Edinburgh

1 Newcastle-upon-Tyne

Manchester

1

1

Sheffield

Birmingham

2

Research areas funded SUDEP 2

Cardiff

3

Co-morbidities 5

Exeter

1

1

2 Bath

Warwick Oxford

1

14 London

Cause 12 Diagnosis & Treatment 12

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Proud members of the Association of Medical Research Charities (AMRC) AMRC membership is the hallmark of research funding. It means that we fund high-quality, peer-reviewed work and that our research procedures are audited every five years so that they meet the gold standard.

For universities, government and other funding bodies, AMRC membership is a recognised indicator of quality, and it qualifies our grants for support from the government’s Charity Research Fund, which entitles universities to a 28% increase on our funding. As AMRC members, we also get access to training alongside other research charities to share ideas and keep our processes up-to-date.

Research impact We closely monitor the impact of our grants to ensure that your heart-felt donations support research of the highest quality.

We do this via a reporting platform called ‘Researchfish’, which is used by a growing network of funding bodies and universities in the UK and Europe.

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Researchfish enables our researchers to tell us, in detail, about where their findings have been disseminated and the impact they might have on future epilepsy research, scientists’ careers and, most importantly, people with epilepsy. Often the research we fund is the first step in a long journey to developing new treatments, but this step is crucial.

A good investment Using Researchfish we have recently tracked the successes of research we funded between 2009 and 2015. During this period we spent £3,305,372 on research grants and these have leveraged a further £11,568,068 in follow-on funding from other sources. Every pound invested by Epilepsy Research UK has therefore generated a further £3.50 for epilepsy research.

£1

£3.50

Generated for epilepsy research

This huge return on our investment demonstrates our ability to identify innovative research at an early stage that will ultimately benefit everyone with epilepsy.

Another indicator of the quality of the research we fund is the number of publications that arise from the work.

A total of 89 journal publications have resulted from ERUK grants during the 2009-2015 period, 15 of which are in very high impact journals such as Brain, Nature and Journal of Physiology.

Further evidence of the quality of the work is the number of citations the publications have achieved (i.e. the number of times the publications have been referred to by other researchers in their work). In this case our publications have been cited a total of 1,363 times to date.

1,363 Citations of ERUKfunded research

“This grant has given us the opportunity to directly help families. Many of the parents who participated in this study desperately wanted to know why their child had severe epilepsy, and it has been great to give answers to so many. It has made a real difference to the management of some of the children.”

Professor Angus Clarke, Cardiff University

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A new technique for the diagnosis and treatment of epilepsy ÂŁ139,595 grant awarded in 2012 Principal Investigator: Professor John Terry Institution: University of Exeter Scientific title: Developing computer models to improve the predictive value of routine clinical EEG

Background

Methods

Electroencephalography (EEG) is widely used in the diagnosis of epilepsy, but it relies on a person having a seizure whilst being monitored. This can lead to severe treatment delays, unnecessary anxiety and reduced quality of life.

Here, Professor Terry aimed to refine their models. Their objective was to find out whether the models were able to analyse resting EEGs and:

To try and address this problem, Professor John Terry, at the University of Exeter, has been working alongside neurologists in London to develop computer models that can detect ‘hidden’ information in brain networks, in short resting EEG recordings (during which no seizure has taken place), and accurately identify whether a person has generalised epilepsy.

1. differentiate more accurately between people with and without generalised epilepsy.

2. distinguish, based on differences in brain network properties, between people with focal and generalised epilepsy.

3. identify, based on the activity of neuronal networks, people who have responded to antiepileptic drug (AED) treatment and those who have not.

If successful, the models would have real potential to enhance the diagnosis of epilepsy, and perhaps even allow neurologists to predict a) whether or not a person would respond to an AED, and b) what the best AED treatment for a person might be, thus reducing the time to optimal therapy.

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“This research project was influential in helping to establish a focus on epilepsy research at the University of Exeter. It has also enabled advancement of our understanding of the brain network mechanisms that allow seizures to occur.”

Professor John Terry

Results With regards to aims one and two, the findings are extremely encouraging. The researchers now have a model that can distinguish with considerable accuracy, from resting EEG recordings, groups of people with generalised epilepsy from healthy controls (who do not have epilepsy). Professor Terry reports that in a test of 30 people with epilepsy and 38 without epilepsy, the model had a misdiagnosis rate of less than 5%. This is highly significant, and the team has already been exploring how they might incorporate the model into a clinical device. On the advice of feedback from commercial companies, they intend to develop a working prototype in the near future.

In terms of differentiating between people with focal and generalised epilepsy, the preliminary data obtained through this grant suggest that this should indeed be possible using computer network modelling. Professor Terry was awarded another ERUK project grant in 2015 to progress these findings and we look forward to hearing the outcome.

For a number of reasons, mainly an unexpected lack of viable resting EEG data from before and after AED treatment, it wasn’t possible to make a lot of progress on aim three. However, there has been significant follow-on funding generated from this grant, particularly from the Engineering and Physical Sciences Research Council, which will enable the team to carry out this research.

Significance This grant has further highlighted the potential of computer models as clinical tools for the diagnosis and management of epilepsy. There is a lot more work to be done to establish their full potential, but the funding is in place and the preliminary evidence is encouraging. We are very excited about this work, as it stands to make a real difference to people’s treatment journeys and quality of life.

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A new strategy to protect the brain from seizures £133,755 grant awarded in 2013 Principal Investigator: Professor Matthew Walker Institution: University College London Scientific title: Preventing seizure induced cell death

by NADPH oxidase inhibition and Nrf2 induction

Background

The study

Molecules called reactive oxygen species (ROS) are produced during normal metabolism, but if their levels get too high it can be damaging to cells. There is increasing evidence that ROS play a crucial role in the death of neurons in a variety of conditions, including prolonged and repeated seizures, and that they may contribute to the development of epilepsy following a brain injury. Human epilepsy trials of antioxidants (e.g. vitamin E), which protect against ROS, have so far been disappointing; however, this is likely to be due to a lack of understanding about how ROS are produced in the brain and the most effective ways of targeting them.

In this project, Professor Matthew Walker and colleagues used brain tissue and animal models to investigate how effective more targeted antioxidants (known as AEBSF, TBE-31 and sulforaphane) are at preventing ROS-related damage to neurons. These drug compounds work in two different ways: 1) by blocking the action of an enzyme that produces ROS (AEBSF) and 2) by increasing the activity of a protein called Nrf2, which ‘defends’ cells from ROS damage (TBE-31 and sulforaphane).

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“This research grant has had an enormous impact on the career of my colleague, Dr Kovac, and has enabled her transition from a PhD student to someone leading her own research and research team.”

Professor Matthew Walker

Findings The results show that: 1. activation of Nrf2 (the ‘defence’ protein) with sulforaphane and TBE-31 protected neurons from seizureinduced damage in tissue models.

However, TBE-31 is not able to enter the brain, which means it would be unsuitable clinically. Fortunately, the scientists were able to replace it with a brand new, highly targeted compound called RTA408, which does reach the brain, and found that it protected neurons in both tissue and animal seizure models.

2. blocking a particular enzyme that generates ROS with AEBSF decreased neuronal death in an animal model of status epilepticus.

3. activation of Nrf2 was the more effective way of preventing seizurerelated damage to neurons in both animal and tissue models. However, they also showed that using a third approach of Nrf2 activation combined with “mopping up” of ROS with a drug called N-acetyl cysteine produced an even more significant effect.

4. activation of Nrf2 with RTA-408 after status epilepticus protected against the development of epilepsy in an animal model.

5. activation of Nrf2 with sulforaphane plus ‘mopping up’ of ROS with N-acetyl cysteine modified the development of epilepsy after status epilepticus in animal models.

Significance These findings are very exciting, because, if applicable to humans, it may become possible to reduce the effects of repeated seizures, such as memory problems, and even prevent epilepsy from developing after a brain injury.

Moreover, the drug compounds used in this project are either in clinical use already for other conditions, or being investigated in clinical trials, which would greatly reduce the time before they were available for epilepsy.

Further research will also need to establish: the time that it takes these drugs to act; whether or not they can be used to modify epilepsy that has already been established; and in what types of epilepsy they are most effective.

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The link between stress and seizures ÂŁ29,208 grant awarded in 2014 Principal Investigator: Professor Stafford Lightman Institution: University of Bristol Scientific title: How do stress hormones trigger seizures?

Background

The study

People with epilepsy very often report emotional stress in the lead-up to a seizure; but although the association between stress and seizures is well recognised, the mechanisms for it are still not understood.

During the study the team used rodent and mathematical models to explore how changes in corticosteroid levels (the rodent equivalent to cortisol) alter the electrical activity of neuronal circuits that are known to be associated with seizures.

The steroid hormone cortisol is secreted by the body in spurts over the course of the day, and its levels increase dramatically during stress. Cortisol is known to have major effects on both neuronal activity and on the ways that brain cells communicate, so it could plausibly play a role in seizures. Here, Professor Lightman and colleagues in Bristol and Exeter started to investigate this theory.

More specifically, they recorded the brain activity of rodents with absence epilepsy (AE) via microelectrodes, and then used various methods to increase the animals’ levels of corticosteroid to see how this affected their seizure activity. They also examined the stress response of control (healthy) rodents for comparison.

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“The data acquired from this grant has provided us with valuable information furthering our understanding of how cortisol can trigger epileptic seizures.”

Professor Stafford Lightman

Findings

Significance

When the team analysed their data they found that injecting AE rodents with corticosteroid didn’t have an impact on their seizure occurrence, but that exposing the animals to a loud sound (a way of increasing corticosteroid levels) did slightly increase their seizure frequency. These results indicate that other components of the body’s stress response, for example an increase in adrenaline, are implicated in seizure activity.

These data are very interesting, but not easily explained at this stage. Follow-on funding will help the team to properly unpick the mechanisms underlying the relationship between stress and seizure frequency. This will hopefully lead to new treatments for epilepsy.

The group also found that the activity of corticosteroid was higher in AE rodents than in controls in ‘resting’ conditions, but that the rise in corticosteroid in response to noise stress was not as great as in controls.

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Estimating the risks of antiepileptic drug exposure in the womb: are new methods as reliable as traditional ones? ÂŁ98,160 grant awarded in 2014 Principal Investigator: Dr Rachel Charlton Institution: University of Bath Scientific title: Sensitivity of electronic healthcare data to investigate neurodevelopmental outcomes following prenatal exposure to antiepileptic drugs

Background

The study

For women with epilepsy, pregnancy requires very careful planning, because exposure to some antiepileptic drugs (AEDs) in the womb, valproate in particular, has been linked to an increased chance of birth defects, behavioural problems and delayed cognitive development.

Here, Dr Charlton and colleagues aimed to compare the two methods, looking at the risk of specific neurodevelopmental disorders associated with different types of AED exposure in the womb.

Traditional methods for assessing the risk of behavioural and developmental issues in unborn babies (i.e. face-to-face interviews) require a lot of work and they are very expensive. In recent years, electronic (e-) databases have increasingly been used instead; however, although this offers many advantages, it is not clear whether it is a reliable way of detecting developmental and behavioural problems.

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The researchers used a recognised e-database to collect information about 7,066 mother-child pairs. Pairs were classified into three groups: 1) the mother had epilepsy and received AED treatment during pregnancy (550) 2) the mother had epilepsy but did not receive AED treatment during pregnancy (468) and 3) the mother did not have epilepsy.

The investigators identified all of the children in each group who had developed a neurodevelopmental disorder, and they were then able to calculate risk estimates.

Risk in the ‘AED-treated group’ was broken down according to the different AEDs/ combinations of AEDs taken by the mothers. Finally, the scientists compared their results with those obtained in an earlier UK study that used traditional methods.

“This research grant has provided a unique opportunity to bring together the necessary expertise to compare two methodologies for determining the risk of neurodevelopmental disorders following in-utero exposure to antiepileptic drugs.”

Dr Rachel Charlton

Findings Both studies found an increased risk of neurodevelopmental disorders in children born to women with epilepsy than in those born to women without epilepsy; however, the database study produced a risk estimate that was much lower.

Unexpectedly, in the database study, neurodevelopmental disorders were found in two children born to women with epilepsy who did not take medication during pregnancy. However, on closer examination it was discovered that these women were still coming off their drugs in the six months before conception, which is likely to have been the cause. To account for these effects, the team adjusted the groups so that the ‘treated’ mothers included women who had taken AEDs in the six months before pregnancy.

In both of the studies, the risk of neurodevelopmental disorders differed between AED exposure groups, and findings were comparable for all bar valproate. Although the database study showed a higher risk with valproate monotherapy (valproate taken alone),

it was a) a lot lower than that seen in the traditional study and b) not statistically significant, even when the exposure groups were modified to include the six months before pregnancy.

Valproate polytherapy (taken with other AEDs) was associated with a significantly increased risk of neurodevelopmental disorders, although this risk was slightly lower than that reported in the traditional study.

Significance These results suggest that neurodevelopmental disorders in children exposed to AEDs before birth are under reported in e-databases. This in turn means that databases might not be as reliable as traditional methods for assessing the risks associated with AED exposure in the womb. Future research must take the findings of this study into consideration, so that women with epilepsy can be offered the most accurate pregnancy advice possible.

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Shaping the future In addition to funding projects at the cutting edge of science, we also have a long-term goal to build the research world of tomorrow. To this end we operate a fellowship programme to bring exceptional young scientists into the field of epilepsy research. Many of our fellows have gone on to make a significant contribution to epilepsy research.

Building the epilepsy research world of

tomorrow

A fantastic example is Dr Andrew Trevelyan, at Newcastle University, who was awarded a fellowship in 2009 to investigate specific mechanisms that underlie seizure activity. Since then he has had outstanding successes, as he describes below:

calcium network imaging, which makes neurons fluorescent when they are excited, we were able to visualise (in rodent models) the activity of individual neurons, and of several hundred neurons at the same time. This gave us a more detailed picture than ever before of how neurons become involved in seizures.’

‘On a personal level, the award of an Epilepsy Research UK fellowship was hugely important, because it gave me the academic freedom to pursue my interest in how seizures spread through the brain. Before that, supported by a US organisation called the Epilepsy Foundation of America, my colleagues and I developed a way to video the spread of epileptic activity in brain tissue that had been kept alive in a dish, fixed to a microscope. Using a cutting-edge technique called

‘During my Epilepsy Research UK fellowship, I wanted to know if these videos could help improve our care of patients with epilepsy. The first step was to learn more about what the videos were showing us. For this I used both the new video technology and more conventional seizure recording methods (tiny electrodes that measure electrical activity), to monitor the same events in rodent brain tissue. I then analysed the different sets of data and tried to match electrical activity to neuronal

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behaviour I was seeing. I gained many new insights into epilepsy in this way, which were very exciting. Firstly, I learnt more about how inhibitory neurons in the brain (that dampen excitation) oppose the spread of epileptic activity. Secondly, I was able to identify the pattern of activity at the very edge of a seizure, and I am now applying this to help develop tools that can pinpoint, in humans, the exact area affected when a seizure takes place. This is fundamental to all surgical epilepsy treatments, because the surgery must target the source of the problem and minimise damage to other brain areas, otherwise there is a risk of doing more damage than good.’

‘The impetus provided by this initial award from Epilepsy Research UK has enabled me to transform my research ambitions. Having been a team of one – myself – at the start of my fellowship, I have since leveraged funds from the MRC, the Wellcome Trust, Epilepsy Research UK (again!) and the BBSRC to build up a team of researchers (currently three postdocs and two PhD students); my publications have been cited over a thousand times; I’ve trained students who have taken up positions in Oxford, New York and Sussex, who in turn have won prestigious fellowships for their own postdoctoral studies; and I’m collaborating with teams across the world.‘ ‘In this way, the seed of funding provided by Epilepsy Research UK at a crucial time in my career has evolved into a major research effort for epilepsy.’

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This year we funded seven exciting new grants, and we are delighted to introduce them here: Dr Gabriele Lignani, University College London A 36-month fellowship has been awarded to Dr Gabriele Lignani, at University College London. The project, entitled ‘GeneLoop: gene therapy activated by seizures to treat epilepsy’, will validate a new method of gene therapy that is only activated in neurons with excessive excitability during seizures (sparing healthy neurons). Ultimately this research may not only develop a cuttingedge approach to stopping seizures it could also enable researchers to better understand which cells in the brain are responsible for triggering seizures and which genes should be ‘targeted’ to stop them. According to Dr Lignani, this new method of gene therapy could potentially reach clinical trials in 5-10 years.

Dr Ivan Pavlov, University College London A 24-month project grant has been awarded to Dr Ivan Pavlov and colleagues, at University College London. Epileptic seizures are caused by excessive activity of groups of neurons in the brain, and many treatments aim to suppress this by increasing inhibitory signalling. Studies in extracted brain tissue have now shown that certain inhibitory neurons that were supposed to stop pathological (disease-causing) ‘firing’ can promote seizure activity; however, it is not clear how this happens, or what its role in living organisms is.

Dr Pavlov and colleagues will conduct research into the ‘role of inhibitory nerve cells

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in seizures’, in which they will investigate this population of cells’ firing activity and their influence on other brain cells. This important project will help us to better understand the mechanisms that underlie epilepsy. This is crucial for the identification of new drug targets and the development of novel therapies.

Dr Rebecca Bromley, University of Manchester Dr Rebecca Bromley and colleagues, at the University of Manchester, have been awarded a 36-month project grant entitled ‘Neurodevelopment after prenatal exposure to seizures (NAPES) study’, in which they will investigate the effects of having seizures during pregnancy on a child’s development.

They hope their findings will enable women with epilepsy to be better placed to make fully informed decisions about the best treatment approach during pregnancy.

Professor Matthew Walker, University College London A 9-month pilot grant, entitled ‘The incidence of hospital admissions with prolonged seizures and status epilepticus in England 1990-2015’, has been awarded to Professor Matthew Walker and colleagues, at University College London.

Status epilepticus is a prolonged seizure (lasting more than five minutes) that requires urgent treatment and hospital admission. It is a significant cause of mortality in people with epilepsy. Since the 1990’s, a lot of work has been carried out to establish care pathways and protocols for status epilepticus/prolonged

seizures, so that all hospitals in the United Kingdom have clear treatment regimens to manage them.

Recent analyses suggest that the death rates for status epilepticus in England and Wales are falling, which may be due to improved/ earlier treatment. However, it is impossible to know this for certain without knowing whether the frequency of status epilepticus has changed in the corresponding period (i.e. it could be that the fall in mortality rate is simply due to fewer cases of status epilepticus in that time). At present, there are no available data on the frequency of status epilepticus in England or indeed whether the frequency of status epilepticus has changed over time.

During this grant, Professor Walker and his colleagues hope to address this gap in knowledge. This will allow for a more informed assessment of current treatment regimens and their effectiveness.

Dr Mark Wall, University of Warwick An 18-month pilot grant entitled ‘Modulation of glial signalling as a novel therapy for absence epilepsy’ has been awarded to Dr Mark Wall and colleagues, at the University of Warwick.

This grant focuses on brain cells called glial cells, which support neurons and are important for maintaining correct communication between them. More specifically, Dr Wall and Dr Richard Ngomba (University of Lincoln) want to find out if a loss of glial cell function is responsible for the increased inhibition that leads to absence seizures. The findings from this project will give important novel information about how absence seizures arise, and they may also reveal new targets for the development of more promising treatments. The methods used will also be useful for the screening process of anti-absence seizure drugs in the

future.

Dr Dora Lozsadi, St George’s Hospital London Dr Dora Lozsadi and colleagues, at St George’s Hospital, London, have been awarded a 12-month pilot grant entitled ‘Recording brain activity using electrodes placed in the nose’. This study aims to assess a new, minimally invasive, technique to monitor brain activity in the frontal lobe of the brain (which can be missed by routine EEG). If successful, the method will significantly improve the diagnosis of frontal lobe epilepsy, allowing people more prompt access to treatment. It will also reduce the need for invasive follow-on investigations and hospital stays.

Dr Stephanie Schorge, University College London A 12-month pilot grant has been awarded to Dr Stephanie Schorge and colleagues, at University College London. The study, entitled ‘What makes some parts of the brain seizure-prone?’, will look at a part of the brain called the hippocampus, which is important in memory function. For reasons that are not fully understood, the front (ventral) end of the hippocampus is much more likely to generate seizures than the back (dorsal) end. Here, Dr Schorge and Dr Gareth Morris will explore why this is the case, so that they can better understand what makes the ventral part so likely to trigger seizures and, in contrast, why the dorsal part is protected. If successful, this project will identify specific features that make the ventral hippocampus so vulnerable to seizures, and, potentially, ways of ‘protecting’ it. In the medium term, this could provide a springboard for the development of new epilepsy treatments that selectively target the ventral hippocampus with minimal side effects.

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Our grant funding process Epilepsy Research UK offers three types of research grant: project grants (£150,000), fellowship awards (£250,000) and pilot grants (£30,000).

We run a competitive annual grant round that involves either one stage of applications (pilot grants) or two stages (project grants and fellowship awards). A call for proposals is circulated in July, with a deadline in September, and short-listing takes place in November.

Each year we receive approximately 60 applications and we award about £700,000 to those of the highest quality.

Final funding decisions are made at the end of March.

All applications are rigorously reviewed by our Scientific Advisory Committee of experts, and shortlisted proposals are also sent for peer review by one to three independent, external reviewers.

The current members of Epilepsy Research UK’s Scientific Advisory Committee are: Mr Alasdair Ball BA (Hons) MBA Head of Collection Management, The British Library Mrs Anne Coxon MSc Currently studying for a health psychology doctorate Professor Mark Cunningham BSc PhD Professor of Neuronal Dynamics, Newcastle University Professor Bruno Frenguelli BSc PhD Professor of Neuroscience, University of Warwick Dr John Livingston MBChB FRCP FRCPH Consultant Paediatric Neurologist, Leeds Teaching Hospitals NHS Trust Dr Adam Noble BSc PhD Tenure Track Fellow, Department of Psychological Sciences, University of Liverpool

Professor Mark Richardson (Chair) MA BMBCh MRCP PhD CCST FRCP Paul Getty III Professor of Epilepsy, Institute of Psychiatry, King’s College London Dr Stephanie Schorge BSc PhD Senior Research Fellow, Department of Clinical & Experimental Epilepsy, Institute of Neurology, University College London Dr Graeme Sills BSc PhD (ex-officio as Chair of Trustees) Senior Lecturer, Division of Neurological Science, University of Liverpool and Walton Centre for Neurology & Neurosurgery Professor Amanda Wood PhD MPsych Chair in Development Neuropsychology, Aston University

For more information, please contact Delphine van der Pauw at delphine@eruk.org.uk, or on 020 8747 5024. All applicants must be affiliated to a recognised UK research institution.

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Thank you Researchers funded by Epilepsy Research UK have made significant contributions in a wide range of areas relating to epilepsy and we are immensely proud of what we have achieved together. We would like to thank all the scientists and clinicians involved in this work towards gaining a greater understanding of epilepsy and a better future for those affected by the condition.

Above all, we would like to thank all the individuals, groups, trusts, foundations and organisations who have contributed to funding the research reported on in this booklet. Without your generous support, none of these achievements would have been possible.

If you would like to support our research or find out more about our work, please visit our website or get in touch with us:

Epilepsy Research UK PO Box 3004 London W4 4XT t 020 8747 5024 e info@eruk.org.uk w www.epilepsyresearch.org.uk

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PO Box 3004 London W4 4XT t 020 8747 5024 e info@eruk.org.uk w www.epilepsyresearch.org.uk Registered in England charity no: 1100394 Report published May 2017