Predicting antiepileptic drug response in children with epilepsy

2011 ◽  
Vol 11 (6) ◽  
pp. 877-886 ◽  
Author(s):  
Matti Sillanpää ◽  
Dieter Schmidt
Keyword(s):  
Antiepileptic Drug ◽  
Drug Response

Predicting the antiepileptic drug response by brain connectivity in newly diagnosed focal epilepsy

2020 ◽  
Vol 267 (4) ◽  
pp. 1179-1187 ◽  
Author(s):  
Kang Min Park ◽  
Kyoo Ho Cho ◽  
Ho-Joon Lee ◽  
Kyoung Heo ◽  
Byung In Lee ◽  
...  
Keyword(s):  
Antiepileptic Drug ◽  
Drug Response ◽  
Focal Epilepsy ◽  
Brain Connectivity ◽  
Newly Diagnosed

scholarly journals Pharmacogenetics of antiepileptic drugs: A brief review

2016 ◽  
Vol 6 (1) ◽  
pp. 28-34 ◽  
Author(s):  
D. Parker ◽  
E. J. Sanders ◽  
K. J. Burghardt
Keyword(s):  
Side Effects ◽  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
International Organizations ◽  
Drug Response ◽  
Genetic Variations ◽  
Clinical Settings ◽  
Patient Response ◽  
Drug Labeling ◽  
Pharmacogenetic Research

Abstract The goal of pharmacogenetic research is to assist clinicians in predicting patient response to medications when genetic variations are identified. The pharmacogenetic variation of antiepileptic drug response and side effects has yielded findings that have been included in drug labeling and guidelines. The goal of this review is to provide a brief overview of the pharmacogenetic research on antiepileptic drugs. It will focus on findings that have been included in drug labeling, guidelines, and candidate pharmacogenetic variation. Overall, several genes have been included in guidelines by national and international organizations; however, much work is needed to implement and evaluate their use in clinical settings.

Antiepileptic drug response in temporal lobe epilepsy: A clinical and MRI morphometry study

Neurology ◽  
2010 ◽  
Vol 75 (19) ◽  
pp. 1695-1701 ◽  
Author(s):  
E. Bilevicius ◽  
C. L. Yasuda ◽  
M. S. Silva ◽  
C. A. M. Guerreiro ◽  
I. Lopes-Cendes ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Antiepileptic Drug ◽  
Temporal Lobe ◽  
Drug Response ◽  
Mri Morphometry

scholarly journals Whole genome sequencing identifies putative associations between genomic polymorphisms and clinical response to the antiepileptic drug levetiracetam

2019 ◽  
Author(s):  
DV Vavoulis ◽  
AT Pagnamenta ◽  
SJL Knight ◽  
MM Pentony ◽  
M Armstrong ◽  
...  
Keyword(s):  
Antiepileptic Drug ◽  
Whole Genome Sequencing ◽  
Clinical Response ◽  
Genome Sequencing ◽  
Drug Response ◽  
Low Frequency ◽  
Response Variability ◽  
Whole Genome ◽  
Extreme Response ◽  
Synaptic Neurotransmission

ABSTRACTIn the context of pharmacogenomics, whole genome sequencing provides a powerful approach for identifying correlations between response variability to specific drugs and genomic polymorphisms in a population, in an unbiased manner. In this study, we employed whole genome sequencing of DNA samples from patients showing extreme response (n=72) and non-response (n=27) to the antiepileptic drug levetiracetam, in order to identify genomic variants that underlie response to the drug. Although no common SNP (MAF>5%) crossed the conventional genome-wide significance threshold of 5×10−8, we found common polymorphisms in genes SPNS3, HDC, MDGA2, NSG1 and RASGEF1C, which collectively predict clinical response to levetiracetam in our cohort with ∼91% predictive accuracy (∼94% positive predictive value, ∼85% negative predictive value). Among these genes, HDC, NSG1, MDGA2 and RASGEF1C are potentially implicated in synaptic neurotransmission, while SPNS3 is an atypical solute carrier transporter homologous to SV2A, the known molecular target of levetiracetam. Furthermore, we performed gene- and pathway-based statistical analysis on sets of rare and low-frequency variants (MAF<5%) and we identified associations between genes or pathways and response to levetiracetam. Our findings include a) the genes PRKCB and DLG2, which are involved in glutamatergic neurotransmission, a known target of anticonvulsants, including levetiracetam; b) the genes FILIP1 and SEMA6D, which are involved in axon guidance and modelling of neural connections; and c) pathways with a role in synaptic neurotransmission, such as WNT5A-dependent internalization of FZD4 and disinhibition of SNARE formation. Targeted analysis of genes involved in neurotransmitter release and transport further supports the possibility of association between drug response and genes NSG1 and DLG2. In summary, our approach to utilise whole genome sequencing on subjects with extreme response phenotypes is a feasible route to generate plausible hypotheses for investigating the genetic factors underlying drug response variability in cases of pharmaco-resistant epilepsy.AUTHOR SUMMARYLevetiracetam (LEV) is a prominent antiepileptic drug prescribed for the treatment of both focal and generalised epilepsy. The molecular mechanism mediating its action is not well understood, but it involves the modulation of synaptic neurotransmition through binding to the synaptic vesicle glycoprotein SV2A. Identifying genomic polymorphisms that predict response to the drug is important, because it can help clinicians prescribe the most appropriate treatment in a patient-specific manner. In this study, we employed whole genome sequencing (WGS) of DNA samples from extreme responders or non-responders to LEV and we identified a small group of common variants, which successfully predict response to the drug in our cohort. These variants are mostly located in genes implicated in synaptic function. Furthermore, we identified significant associations between clinical response to LEV and low-frequency variants in genes and pathways involved in excitatory neurotransmission or in the moulding of neural networks in the brain. Our approach to utilise WGS on subjects with extreme response phenotypes is a feasible route to generate plausible hypotheses on the genomic basis of pharmaco-resistant epilepsy. We expect that the rapidly decreasing cost of WGS will allow conducting similar studies on a larger scale in the near future.

scholarly journals Biomarkers for antiepileptic drug response

2011 ◽  
Vol 5 (5) ◽  
pp. 635-641 ◽  
Author(s):  
Tracy A Glauser
Keyword(s):  
Antiepileptic Drug ◽  
Drug Response

The -1021C->T DBH gene variant is not associated with epilepsy or antiepileptic drug response

Neurology ◽  
2004 ◽  
Vol 63 (8) ◽  
pp. 1497-1499 ◽  
Author(s):  
C. Depondt ◽  
H. R. Cock ◽  
D. G. Healy ◽  
M. W. Burley ◽  
D. Weinshenker ◽  
...  
Keyword(s):  
Antiepileptic Drug ◽  
Drug Response ◽  
Gene Variant

Clinical factors and ABCB1 polymorphisms in prediction of antiepileptic drug response: a prospective cohort study

2006 ◽  
Vol 5 (8) ◽  
pp. 668-676 ◽  
Author(s):  
Guy Leschziner ◽  
Andrea L Jorgensen ◽  
Munir Pirmohamed ◽  
Paula R Williamson ◽  
Anthony G Marson ◽  
...  
Keyword(s):  
Cohort Study ◽  
Antiepileptic Drug ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Drug Response ◽  
Clinical Factors

Impact of ABCC2 genotype on antiepileptic drug response in Caucasian patients with childhood epilepsy

2011 ◽  
Vol 21 (10) ◽  
pp. 624-630 ◽  
Author(s):  
Mike Ufer ◽  
Celina von Stülpnagel ◽  
Hiltrud Muhle ◽  
Sierk Haenisch ◽  
Cornelia Remmler ◽  
...  
Keyword(s):  
Antiepileptic Drug ◽  
Drug Response ◽  
Childhood Epilepsy ◽  
Caucasian Patients
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