Biomarkers in epilepsy-A modelling perspective

Abstract

Biomarkers can be categorised from type 0 (genotype or phenotype), through 6 (clinical scales), each level representing a part of the processes involved in the biological system and drug treatment. This classification facilitates the identification and connection of information required to fully (mathematically) model a disease and its treatment using integrated information from biomarkers. Two recent reviews thoroughly discussed the current status and development of biomarkers for epilepsy, but a path towards the integration of such biomarkers for the personalisation of anti-epileptic drug treatment is lacking. Here we aim to 1) briefly categorise the available epilepsy biomarkers and identify gaps, and 2) provide a modelling perspective on approaches to fill such gaps. There is mainly a lack of biomarker types 2 (target occupancy) and 3 (target activation). Current literature typically focuses on qualitative biomarkers for diagnosis and prediction of treatment response or failure, leaving a need for biomarkers that help to quantitatively understand the overall system to explain and predict differences in disease and treatment outcome. Due to the complexity of epilepsy, filling the biomarker gaps will require collaboration and expertise from the fields of systems biology and systems pharmacology.

Keywords: Biomarkers; Disease progression; Individualised medicine; Personalised medicine; Physiology-based models; Systems biology; Systems pharmacology.