SPEAKERS:

• Christophe Bernard (Marseille, FR)

The circadian and multidien rhythmicity of seizures

Clinical data demonstrate that >80% of patients present periods of enhanced seizure probability during the circadian cycle. In addition, a majority of patients present a slower rhythmicity of seizures over days and weeks (multidien). Dogs and rodents with spontaneous seizures present similar features, suggesting that these rhythms represent core biological processes, which are perhaps universal. The discovery that the molecular architecture of neuronal networks oscillate in a circadian manner provides a conceptual framework to understand the rhythmicity of seizures. This opens new possibilities to understand seizure mechanisms and design novel treatments in the context of chronotherapy.

• Cristina Ruedell Reschke (Dublin, IE)

Short non-coding RNAs

The epileptogenesis process is associated with large-scale changes in gene expression, which contribute to the remodeling of brain networks permanently altering excitability. These impactful changes are largely regulated by small non-coding RNAs (sncRNAs), especially by microRNAs. In the brain, microRNAs are required for cell growth, differentiation, and synaptic plasticity as well as the control of neuroinflammation and apoptosis. Notably, many of these processes are dysregulated in epileptogenesis. Targeting key microRNAs has been shown to alter brain excitability and suppress or exacerbate seizures, indicating therapeutic potential. Biofluid microRNA profile may support both diagnostics development and therapeutic drug monitoring. Other sncRNAs remain poorly explored. In-depth understanding of scnRNAs role in epilepsy holds the promise to represent an important step-stone for advancing precision therapeutics.

• Annamaria Vezzani (Milan, IT)

Innate immunity and inflammation in epilepsy

The increasing elucidation of the complexity and dynamics of neuroinflammation in epilepsy has generated potential cellular and molecular targets for developing new drugs, or for repurposing available anti-inflammatory drugs, acting on key pathogenic mechanisms. This approach to therapy should overcome the mere symptomatic control of seizures which is attained with the current medications. Proof-of-concept clinical studies have indeed shown that specific anti-inflammatory interventions are endowed of therapeutic effects in animal models of acquired epilepsies, and reduce seizures in epilepsy patients who are resistant to current antiseizure medications.

• Michele Simonato (Ferrara and Milan, IT)

Gene therapy

Gene therapy has recently advanced to the level of standard of care for several diseases, but its application to neurological disorders is still in the experimental phase. However, patients with partial epilepsies selected for surgical resection of the epileptogenic area are ideal candidates for gene therapy because brain pathology is focal, medical treatment has failed, and gene transfer of seizure-inhibitory factors into the seizure-generating area might silence epileptic hyperactivity. In the event that gene therapy fails to prevent seizures, patients could undergo surgery as originally planned. Recent advancements in the field provide optimism on the possibility to have first-in-human studies for gene therapy of some forms of epilepsy in the not-so-distant future.

MODERATOR:

• Micaela Morelli (Cagliari, IT)