PGXOME · A pharmacogenomic exploration of adverse drug reactions in epilepsy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2017-09-01 → 2018-08-31
- EU contribution
- €82,799
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
A pharmacogenomic exploration of adverse drug reactions in epilepsy
The aim of this project is to enhance our understanding of the genetic factors that underlie the risk for adverse drug reactions (ADRs) to anti-epileptic drugs (AEDs). Epilepsy is a common disease characterized by recurrent seizures affecting 50 million people worldwide. For most people with epilepsy, long term treatment with AEDs are necessary and 40% do not respond to the first drug, leading to a lifelong odyssey towards effective treatment. Further, for each AED a person is treated with there is a considerable risk that they will have a serious and intolerable side-effect. ADRs can be minimized by careful titration towards therapeutic dose however some rare ADRs, particularly the various skin rash and hypersensitivity syndromes, have been shown to have a genetic component. It is hoped that the results of this project will provide clinically useful genetic markers of ADRs that can be used by clinicians to screen people with epilepsy and help prescribe optimal, safe treatment targeted to the individual thereby improving medication safety in epilepsy.
Data: CORDIS, © European Union
Project objective
Epilepsy is a common disease characterized by recurrent seizures affecting 50 million people worldwide. For most people with epilepsy, long term treatment with antiepilepileptic drugs (AEDs) are necessary and 40% do not respond to the first line of AED, leading to a lifelong odyssey towards effective treatment. Diagnosis is the only predictor of which drug will work best however it is a poor predictor and there is a need for improved biomarkers. AEDs carry a considerable risk for adverse drug reactions (ADRs). ADRs can be minimized by careful titration towards therapeutic dose however idiosyncratic ADRs, particularly cutaneous adverse reactions, have been shown to have a genetic predisposition. However, despite the relative success of GWAS to identify predictors of hypersensitivity there are few other predictors of some more common ADRs. The applicant is aligned with large international consortia such as EpiPGX, the International League Against Epilepsy (ILAE) Complex Genetics Consortium and the the Canadian Pharmacogenetic Network for Drug Safety (CPNDS) who have amassed a collection of over 15,000 epilepsy cases with phenotype and genotype data. Further, over 2000 samples have whole exome sequence data available. This has provided a medium to investigate the genetic architecture of ADRs and a resource to replicate novel significant findings. This fellowship proposes to move beyond traditional GWAS into new territory for epilepsy pharmacogenomics by exploring the contribution of polygenic risk and rare variants. The aim of this fellowship proposal is to identify clinically useful genetic markers of adverse reactions to AEDs to the growing number of prognostic tests for clinicians to prescribe optimal treatment targeted to each individual patient and improve medication safety in epilepsy.
Original text from CORDIS.
Participants
- UNIVERSITAIR MEDISCH CENTRUM UTRECHT · UtrechtCoordinatorNetherlands
Links
- View on CORDIS
- DOI: 10.3030/751761
- https://www.umcutrecht.nl/en/Research/Other-research/Center-for-Molecular-Medicine/Section-Genetics/Koeleman
Data: CORDIS, © European Union