Precision medicine and therapies of the future

Abstract

Precision medicine in the epilepsies has gathered much attention, especially with gene discovery pushing forward new understanding of disease biology. Several targeted treatments are emerging, some with considerable sophistication and individual‐level tailoring. There have been rare achievements in improving short‐term outcomes in a few very select patients with epilepsy. The prospects for further targeted, repurposed, or novel treatments seem promising. Along with much‐needed success, difficulties are also arising. Precision treatments do not always work, and sometimes are inaccessible or do not yet exist. Failures of precision medicine may not find their way to broader scrutiny. Precision medicine is not a new concept: It has been boosted by genetics and is often focused on genetically determined epilepsies, typically considered to be driven in an individual by a single genetic variant. Often the mechanisms generating the full clinical phenotype from such a perceived single cause are incompletely understood. The impact of additional genetic variation and other factors that might influence the clinical presentation represent complexities that are not usually considered. Precision success and precision failure are usually equally incompletely explained. There is a need for more comprehensive evaluation and a more rigorous framework, bringing together information that is both necessary and sufficient to explain clinical presentation and clinical responses to precision treatment in a precision approach that considers the full picture not only of the effects of a single variant, but also of its genomic and other measurable environment, within the context of the whole person. As we may be on the brink of a treatment revolution, progress must be considered and reasoned: One possible framework is proposed for the evaluation of precision treatments.

The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond

“…More recently, novel epilepsy therapies have been developed that act by disease-specific mechanisms, including everolimus (inhibition of mTOR signaling in TSC) and cerliponase alfa (for lysosomal enzyme replacement in neuronal ceroid lipofuscinosis type 2) [38]. The latter treatments are examples of "precision medicine," a relatively new area of disease-specific therapies that may revolutionize the therapy of genetic epilepsies [128]. Indeed, there is now cause for optimism that we are entering a new paradigm where it will be possible to engineer specific treatments for some genetically defined epilepsies using disease-mechanism-targeted small molecules, antisense, gene therapy with viral vectors, and other biological approaches [38].…”

Carbon emission savings and short‐term health care impacts from telemedicine: An evaluation in epilepsy

“…Focusing on the most vulnerable in society, rather than national averages, as a measure of policy success, will be important 31 . Such a nuanced and individual approach will add a layer of “climate considerations” to the growing push to precision medicine in epilepsy 32 …”

Potential for improved retention rate by personalized antiseizure medication selection: A register‐based analysis

“…There is seldom enough information beforehand on which ASM will be most effective in the individual patient. Personalized medicine, a concept referring to the prediction of treatment effectiveness based on the characteristics of an individual patient, is not yet possible but greatly needed in epilepsy 4‐8 …”