Helbig I, Ellis CA. Personalized medicine in genetic epilepsies - possibilities, challenges, and new frontiers. Neuropharmacology. 2020 Aug 1;172:107970. doi: 10.1016/j.neuropharm.2020.107970. Epub 2020 Jan 20. PMID: 32413583.
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.
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