A roadmap for precision medicine in the epilepsies

Abstract

Technological advances have paved the way for accelerated genomic discovery and are bringing precision medicine clearly into view. Epilepsy research in particular is well suited to serve as a model for the development and deployment of targeted therapeutics in precision medicine because of the rapidly expanding genetic knowledge base in epilepsy, the availability of good in-vitro and in-vivo model systems to efficiently study the biological consequences of genetic mutations, the ability to turn these models into effective drug-screening platforms, and the establishment of collaborative research groups. Moving forward, it is crucial that these collaborations are strengthened, particularly through integrated research platforms, to provide robust analyses both for accurate personal genome analysis and gene and drug discovery. Similarly, the implementation of clinical trial networks will allow the expansion of patient sample populations with genetically defined epilepsy so that drug discovery can be translated into clinical practice.

Figure 1

Estimated proportion of individuals with different types of epilepsy who carry a strong-acting, single mutation that either contributes substantially to or causes epilepsy. Source: Kalachikov et al (2002), EuroEPINOMICS-RES Consortium, Epilepsy Phenome/Genome Project, Epi4k Consortium (2014), Epilepsy Phenome/Genome Project Epi4K Consortium (2015), Mefford et al (2011), Olson et al (2014), Dibbens et al (2013), Ishida et al (2013), Picard et al (2014), and Thomas et al (2014).

Figure 2

Genes known to be associated with epilepsy, broken out by those with relevant in-vitro models and those with research support from family foundations (A) List of known epilepsy genes. (B) The estimated percentage of epilepsy genes for which an in-vitro assay is available to accurately assess the effects of mutations (in red). (C) The percentage of epilepsy genes for which research is actively being driven by family foundations (in red).

Figure 3

Current practice for genetic diagnosis in epilepsy and the envisioned future of precision medicine in epilepsy (A) Current practice for genetic diagnosis in epilepsy. (B) New additions to the approach of precision medicine are highlighted in purple boxes. In the envisioned model of precision medicine in epilepsy, all types of non-acquired epilepsy will be assessed, and basic, clinical, and translational science will be closely integrated to drive the development of precision therapies.