Novel treatment perspectives from advances in understanding of genetic epilepsy syndromes

ABSTRACT

Introduction: It is increasingly clear that epilepsy is genetically heterogeneous and novel gene discoveries have moved the field beyond the known contribution of ion channels to implicate chromatin remodeling, transcriptional regulation and regulation of cortical development. Although such discoveries pave the way for new therapeutics, relatively little has been written on the potential implications for treatment. We discuss the most recent advances in the field of epilepsy genetics, as facilitated by genomic technologies, and highlight several novel molecular targets and and potential novel therapeutic strategies.

Areas covered: Epilepsy molecular mechanisms, genetic epilepsies, novel therapeutic approach.

Expert opinion: The genetic confirmation and classification of a clinical diagnosis in an individual provides certainty in treatment decisions, prognosis, and evaluation of seizure recurrence risks and may also prevent unnecessary diagnostic investigations. The growing number of discoveries on this topic may lead to targeted therapeutic approaches in the near future. Only better understanding of mechanisms of epilepsies can result in great improvement of therapy and quality of life of patients.

KEYWORDS:

• Epilepsy
• genetics
• antiepileptic drugs
• therapy
• precision medicine
• review

Article highlights

• Despite the availability of numerous drug options, treatment is still challenging in about one third of the epilepsy patients and it may lead to a severe medically, physically, and socially disabling condition.

• Advances in genomic technologies that facilitate genome-wide discovery of both common and rare variants have led to a rapid increase in our understanding of epilepsy genetics.

• Novel gene discoveries have moved the field beyond the known contribution of ion channels to implicate chromatin remodeling, transcriptional regulation, and regulation of brain development in the etiology of epilepsy.

• The novel genetic methods may lead to discover novel therapeutic avenues and individualized (precision) medicine that is expected to greatly improve the management of patients.

• The biggest challenge in the field of therapy of genetic epilepsies certainly is prevention of epileptogenesis (i.e. antiepileptogenesis).

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.