Study offers hope of better epilepsy treatments
There are 50 million people worldwide with epilepsy - 600,000 in the UK - with the mainstay of treatment being anti-epileptic drugs. But 30 per cent of those people do not respond to these drugs and continue to have seizures. Even when a person's seizures are brought under control, they may often experience side effects including fatigue, memory loss, weight gain and irritability.
EpiPGX is a multi-centre European Union funded project which has been focusing on the way genetic variants can determine a person's response to anti-epileptic drugs. Led by Epilepsy Society's director of clinical genetics and professor of neurology at UCL, Sanjay Sisodiya, scientists from a consortium of 15 European centres have been trying to identify genome-based indicators that will allow them to accurately predict who will respond well to which drug, at which dose and with the least possible side effects.
At the final meeting of the consortium in London (above), chief investigator Professor Sisodiya said that although they were at the end of the funded period of the project, they had now reached the most exciting stage as they would begin to analyse data accumulated over the last four years.
'We have collated a database of almost 10,000 people with epilepsy and this is likely to rise to 12,000 which must be one of the biggest sets of data of this type in the world,' he said.
'In the coming years we will be mining and exploring this database, using genome-wide analyses to identify genetic variations that may influence a person's response to anti-epileptic drugs.
'At the moment we cannot predict which drug to try for which person at which dose, nor which drug to avoid. EpiPGX is trying to understand the genetics underlying individual drug response. We hope that this will help us in our quest to deliver the right drug, at the right dose, from the point of diagnosis.
Genetic variants in epilepsy
EpiPGX has been investigating genetic variants that could indicate:
- early treatment response in newly-diagnosed epilepsy
- chronic resistance to anti-epileptic drugs
- late response to specific anti-epileptic drugs
- specific adverse drug reactions
- risk of major congenital malformations in infants exposed to AEDs during pregnancy.
Side effects from epilepsy drugs
Dr Gianpiero Cavalleri from the Royal College of Surgeons in Ireland has been leading on the project to identify whether particular genetic variants may be predictive of a particular adverse reaction. Although he is still cautious about early results, his group has discovered evidence which may suggest two new genetic indicators for adverse drug reactions. The first on chromosome 1 is for a skin rash linked to phenytoin. The second is for behavioural disorders associated with levetiracetam
'It is early days yet and there is more work to be done, but the results are quite exciting,' said Dr Cavalleri.'
Dr Graeme Sills of the University of Liverpool said that their research into early treatment response was already showing non-genetic indicators for likely outcomes. Clinical factors positively associated with early seizure control after one epilepsy drug included: older age, generalised tonic clonic seizures only and generalised epilepsy. Clinical factors associated with poor response after a first anti-epileptic drug included: abnormal neurological test results, higher number of seizures prior to treatment and some abnormalities on MRI.
Power of European collaboration
Professor Sanjay Sisodiya said: 'EpiPGX is a great example of what can be achieved when doctors and scientists from across Europe collaborate. We now have a rich data set that will lead to more and more analysis and a better understanding of the genetics underlying drug response.
'Recurrent seizures impair the quality of life for people with epilepsy. I hope the work of EpiPGX will help us to get the right treatment to the right people at the right time.'