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Personalized medicine in genetic epilepsies - possibilities, challenges, and new frontiers.
Neuropharmacology. 2020 Aug 01; 172:107970.N

Abstract

Identifying the optimal treatment based on specific characteristics of each patient is the main promise of precision medicine. In the field of epilepsy, the identification of more than 100 causative genes provides the enticing possibility of treatments targeted to specific disease etiologies. These conditions include classical examples, such as the use of vitamin B6 in antiquitin deficiency or the ketogenic diet in GLUT1 deficiency, where the disease mechanism can be directly addressed by the selection of a specific therapeutic compound. For epilepsies caused by channelopathies there have been advances in understanding how the selection of existing medications can be targeted to the functional consequences of genetic alterations. We discuss the examples of the use of sodium channel blockers such as phenytoin and oxcarbazepine in the sodium channelopathies, quinidine in KCNT1-related epilepsies, and strategies in GRIN-related epilepsies as examples of epilepsy precision medicine. Assessing the clinical response to targeted treatments of these conditions has been complicated by genetic and phenotypic heterogeneity, as well as by various neurological and non-neurological comorbidities. Moving forward, the development of standardized outcome measures will be critical to successful precision medicine trials in complex and heterogeneous disorders like the epilepsies. Finally, we address new frontiers in epilepsy precision medicine, including the need to match the growing volume of genetic data with high-throughput functional assays to assess the functional consequences of genetic variants and the ability to extract clinical data at large scale from electronic medical records and apply quantitative methods based on standardized phenotyping language.

Authors+Show Affiliations

Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA; The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA; Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA. Electronic address: helbigi@email.chop.edu.The Epilepsy NeuroGenetics Initiative (ENGIN), Children's Hospital of Philadelphia, Philadelphia, USA; Department of Biomedical and Health Informatics (DBHi), Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA; Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32413583

Citation

Helbig, Ingo, and Colin A. Ellis. "Personalized Medicine in Genetic Epilepsies - Possibilities, Challenges, and New Frontiers." Neuropharmacology, vol. 172, 2020, p. 107970.
Helbig I, Ellis CA. Personalized medicine in genetic epilepsies - possibilities, challenges, and new frontiers. Neuropharmacology. 2020;172:107970.
Helbig, I., & Ellis, C. A. (2020). Personalized medicine in genetic epilepsies - possibilities, challenges, and new frontiers. Neuropharmacology, 172, 107970. https://doi.org/10.1016/j.neuropharm.2020.107970
Helbig I, Ellis CA. Personalized Medicine in Genetic Epilepsies - Possibilities, Challenges, and New Frontiers. Neuropharmacology. 2020 Aug 1;172:107970. PubMed PMID: 32413583.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Personalized medicine in genetic epilepsies - possibilities, challenges, and new frontiers. AU - Helbig,Ingo, AU - Ellis,Colin A, Y1 - 2020/01/20/ PY - 2019/08/11/received PY - 2020/01/05/revised PY - 2020/01/16/accepted PY - 2020/5/16/pubmed PY - 2020/5/16/medline PY - 2020/5/16/entrez KW - Electronic medical records KW - Epilepsy KW - Human phenotype ontology KW - Neurogenetics KW - Precision medicine SP - 107970 EP - 107970 JF - Neuropharmacology JO - Neuropharmacology VL - 172 N2 - Identifying the optimal treatment based on specific characteristics of each patient is the main promise of precision medicine. In the field of epilepsy, the identification of more than 100 causative genes provides the enticing possibility of treatments targeted to specific disease etiologies. These conditions include classical examples, such as the use of vitamin B6 in antiquitin deficiency or the ketogenic diet in GLUT1 deficiency, where the disease mechanism can be directly addressed by the selection of a specific therapeutic compound. For epilepsies caused by channelopathies there have been advances in understanding how the selection of existing medications can be targeted to the functional consequences of genetic alterations. We discuss the examples of the use of sodium channel blockers such as phenytoin and oxcarbazepine in the sodium channelopathies, quinidine in KCNT1-related epilepsies, and strategies in GRIN-related epilepsies as examples of epilepsy precision medicine. Assessing the clinical response to targeted treatments of these conditions has been complicated by genetic and phenotypic heterogeneity, as well as by various neurological and non-neurological comorbidities. Moving forward, the development of standardized outcome measures will be critical to successful precision medicine trials in complex and heterogeneous disorders like the epilepsies. Finally, we address new frontiers in epilepsy precision medicine, including the need to match the growing volume of genetic data with high-throughput functional assays to assess the functional consequences of genetic variants and the ability to extract clinical data at large scale from electronic medical records and apply quantitative methods based on standardized phenotyping language. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/32413583/Personalized_medicine_in_genetic_epilepsies_-_possibilities,_challenges,_and_new_frontiers L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(20)30036-8 DB - PRIME DP - Unbound Medicine ER -
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