Novel approaches for epilepsy therapy: current and emerging research frontiers

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Background

Epilepsy is a devastating neurological disorder characterized by recurrent seizures, which, according to the Institute of Medicine 2012 report, will affect 1 in 26 people over their lifetime and actively affects 1% of the general population at a given time.

Epilepsy cannot be considered a single disease, but must be regarded instead as a family of disorders with different etiologies, symptoms and progression. Different types of epileptic seizures arise from focal dysfunction of different cell populations in different brain areas. Seizure foci are typically characterized by structural neural network rearrangements, and a functional imbalance between excitation and inhibition, in favor of increased excitability.

To experimentally address the structural and functional changes associated with epilepsies requires advanced tools and oftentimes complex approaches. Even then, identifying signaling
mechanisms or neuronal populations that could serve as targets for therapeutic intervention remains a formidable task. New technologies are needed to provide innovative ways to target
abnormal pathways without affecting other cells or brain regions needed for normal cognitive function.

Over the last years, the emergence of several novel research approaches has opened unprecedented possibilities for the study of disease processes and the potential for novel interventions. The development of optogenetics and chemogenetics has enabled the investigation of specific connections within complex networks, and increased our understanding of how certain cell populations in epileptic tissues contribute to the generation of seizures. In
addition, optogenetic and chemogenetic techniques are being developed towards therapeutic applications, and show promise for some types of epilepsy.

Moreover, the refinement of super­resolution microscopy techniques, including multiphoton microscopy, Stimulated Emission Depletion (STED) and STochastic Optical Reconstruction Microscopy (STORM), now enables researchers to study anatomical features in greater detail. This could help to identify morphological alterations or changes in protein nanoscale distribution, which might be important during epileptogenic processes. Further, new developments in the field of gene editing, including CRISPR/Cas9, provide great possibilities for interfering with the expression of specific genes at defined time points during
epileptogenesis or at the chronic epileptic state, to identify and dissect critical genes and period that affect the development and maintenance of epilepsy.

This research topic seeks to collect original research articles, reviews, and methodological/technological papers pertaining the use of novel research approaches for the study of epilepsy. The focus is placed on experimental work that has the potential to contribute in the development of novel therapies against pharmacoresistant epilepsy.

Keywords: Epilepsy, Optogenetics, Microscopy, Gene therapy, Gene editing

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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