EPIPGX

Epilepsy Pharmacogenomics: delivering biomarkers for clinical use

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 Obiettivo del progetto (Objective)

'The purpose of the project is to identify genome-based biomarkers for use in clinical practice to individualise treatment of epilepsy, and stratify patients for clinical trials, aiming to avoid chronicity, prevent relapse and reduce adverse drug reactions (ADRs). The need for improved treatments in epilepsy is undoubted. Epilepsy is affects 50,000,000 people of all ages worldwide. Epilepsy is serious, increasing morbidity across all aspects of life, including a high risk of premature mortality. Over 20 antiepileptic drugs (AEDs) are licenced for its treatment. Seizures can be effectively controlled by AEDs in ~70% of people. Control of seizures leads to risk reduction for most of consequences of epilepsy, improves quality of life, permits social re-integration and leads to direct economic benefits. However, in 30% of patients, currently-available AEDs do not control seizures – recurrent seizures threaten life and impair its quality in these patients, and account for much of the €15.5 billion annual cost of epilepsy in the EU alone; there is currently no way to predict which patients will not respond to any or all AEDs; even in the 70% who do respond, only 47% respond to the first AED – whilst the correct drug is being sought, risks from seizures continue – we need to be able to predict the right drug for an individual from the outset; unrelated to responder status, AEDs can cause serious ADRs – a biomarker exists for only one ADR; there is a clear need for novel means of discovery of new AEDs – existing AEDs are anti-seizure drugs, not disease-modifying drugs. We will use genome-wide analyses, including next-generation sequencing, in large, well-phenotyped patient cohorts to identify genome-based biomarkers, to improve use of current AEDs and identify new therapy targets. SMEs, which are central to this project, will be able to take the data forward for development of clinical tests; data will also be invaluable for industry seeking to develop new treatments.'

Introduzione (Teaser)

For any disease, treatment should present minimal adverse effects and maximum therapeutic outcome. To achieve this, a European study is working on genomic biomarkers that predict treatment response in epilepsy.

Descrizione progetto (Article)

Epilepsy is a neurological condition that affects nearly fifty million people worldwide. It increases morbidity across all aspects of life and also presents an increased risk of premature mortality.

There are over 20 antiepileptic drugs (AEDs) licensed for treatment that successfully control seizures in most patients, improving their quality of life and permitting social re-integration. However, for nearly 30 % of patients AEDs are not effective, necessitating the development of new treatment modalities. Also, ideally interventions should be disease-modifying rather than merely controlling seizures.

The EU-funded http://www.epipgx.eu/ (EPIPGX) (Epilepsy pharmacogenomics: delivering biomarkers for clinical use) study proposes to perform genome-wide analyses to identify genome-based biomarkers for epilepsy. The aim is to predict treatment response thereby improving the use of current AEDs and also identifying new therapy targets. Partners focused on the impact of the AEDs most commonly prescribed in the EU and those that incur huge healthcare costs.

During the initial phase of the project, scientists extracted data from over 5,000 clinical cases and genotyped nearly 8,000 samples. Genome-wide association studies for broad drug resistance and AED adverse reactions is also ongoing. Exome sequencing will also offer information on rare genetic variation that may influence AED treatment.

Collective analysis of these datasets should provide pharmacogenomic guidance to avoid serious adverse effects and help clinicians select the best-tolerated AEDs. Special emphasis will also be given on identifying biomarkers of teratogenesis that are associated with the use of the drug valproate in pregnancy.

Furthermore, the consortium is interested in developing an in silico method to predict the best treatments and outcomes for individual patients. This platform is anticipated to attract great interest from the industry.

Overall, the identification of biomarkers that can predict the pattern of response to AEDs will be of high clinical importance for people with newly-diagnosed and chronic epilepsy. In addition, it should optimise clinical management of people with epilepsy, improve treatment outcome and lead to new potential therapeutic targets.