Refractory Juvenile Myoclonic Epilepsy Cohort (ReJuMEC)

Lead Research Organisation: University of Liverpool
Department Name: Clinical Sciences

Abstract

Juvenile myoclonic epilepsy (JME) is a type of epilepsy which is usually diagnosed in the teenage years. There are an estimated 45,000 people with JME in the UK. People with JME often have three different types of seizures, brief muscle jerks usually of the upper limbs (myoclonus), convulsions, and short periods of impaired awareness (absence seizures). JME is a lifelong disorder which requires treatment with antiepileptic drugs but this is only effective in 70% of people. In the remainder, one or more of the seizure types persists despite drug treatment and this can lead to reduced educational attainment and employment opportunities, social stigma, an inability to drive, difficulty in forming relationships, and a dependence on others for daily care. It is estimated that one in every two hundred people with uncontrolled epilepsy will die as a result of their seizures. Treatment options for people with JME are limited and new drugs are not usually developed for this condition. Most are tested for other types of epilepsy and only become available for JME by chance. This reduces the likelihood that they will be effective. This project will bring together a group of epilepsy experts from across the UK in order to identify 200 people with drug resistant JME from out-patient clinics. The clinical records of these patients will be reviewed in detail and they will undergo further tests aimed at better understanding their disease. All information will be stored on a secure, centralised database at the University of Liverpool and will be used by UK researchers to investigate the causes and consequences of JME. As a result, patients will have the opportunity to take part in other research projects and to become involved in drug trials of new epilepsy medications. It is anticipated that the availability of a large group of people with well-defined JME will encourage the pharmaceutical industry to develop new treatments specifically for this type of epilepsy. The ultimate aim of this project is to raise awareness of JME, to improve understanding of its causes, and to find new treatments for this common and often debilitating epilepsy which increase the likelihood that people with JME can live a life free from seizures.

Technical Summary

We will establish a cohort of patients with drug refractory juvenile myoclonic epilepsy (JME). This will help alleviate bottlenecks in the development of new treatments for JME and facilitate novel studies of basic disease mechanisms. Juvenile myoclonic epilepsy (JME) is a common idiopathic epilepsy syndrome which accounts for approximately 10% of all epilepsies presenting in adolescence and early adulthood. JME is characterised by the presence of a triad of seizure types, myoclonic seizures, generalised tonic clonic seizures and absence seizures, and an EEG which typically shows generalised polyspike and wave abnormalities. Sodium valproate is the treatment of choice and is effective in around 70% of JME patients. The remainder continue to experience regular seizures, with a detrimental impact on their physical and psychosocial wellbeing and an increased risk of sudden unexpected death. Other treatment options for JME are limited, predominantly because current trends in novel drug development for epilepsy favour focal epilepsies. Although idiopathic generalised epilepsies account for 40% of all human epilepsy, few drugs are ever formally evaluated in this population because of the difficulty in assembling a sufficiently large group of patients with a single syndromic classification. This project will assemble a cohort of 200 people with unresponsive JME from across the UK that will be defined on the basis of their clinical and drug histories, EEG characteristics, and neuropsychological profile. A DNA sample will be obtained to facilitate future studies of genetic aetiology. This cohort will serve as an unrivalled resource for the conduct of future multi-centre drug trials in idiopathic generalised epilepsy. Features of JME, such as the presence of multiple seizure types and a characteristic EEG, make it an ideal surrogate for evaluating new treatments with potential efficacy in the wider group of idiopathic generalized epilepsies. Assembly of this cohort will also facilitate neuroimaging and genetics studies designed to better characterise the anatomical, neuronal and molecular substrates which underlie the aetiology of JME and provide a platform for exploration of the longitudinal effects of idiopathic generalised epilepsy and its treatment on memory and cognition. This is a unique endeavour, bringing together multiple expert centres from across the UK, to assemble a highly phenotyped cohort of patients with a single epilepsy syndrome. It will help to maintain the recent tradition of collaborative working practices within the UK epilepsy community and will ultimately benefit people with epilepsy by improving the understanding and treatment of idiopathic generalised epilepsies.
 
Description Epilepsy Research UK project grant
Amount £89,230 (GBP)
Organisation Epilepsy Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start  
 
Description EPI25K 
Organisation Broad Institute
Country United States 
Sector Charity/Non Profit 
PI Contribution US Government has funded Broad as a major sequencing centre, which includes a theme on epilepsy that will exome sequence 6000 epilepsy patients, to which our group will make a major contribution as part of an international consortium
Collaborator Contribution Project design, defining phenotypes and contributing DNA and phenotype data from for sequencing.
Impact Too early, collaboration just established
Start Year 2016
 
Description EPi5 
Organisation Broad Institute
Country United States 
Sector Charity/Non Profit 
PI Contribution EPi25 is an international consortium funded by the NIH in the USA. The aim is to exome and whole genome sequence DNA from patient with epilepsy to identify the genetic predisposition to the condition. The Liverpool group hold the largest cohort with prospective clinical data and DNA. We therefore make a major contribution to this consortium. Marson is a member of the steering committee, and the phenotyping committee.
Collaborator Contribution Partners across the world have provided DNA samples and phenotype data. Broad is leading the sequencing and have sequenced over 500 Liverpool cases and data are now held in Liverpool for further analysis and study.
Impact None yet, too early
Start Year 2016