Basic science can help to “cure” – not just “to control” – epilepsy: the role of neurovascular unit in epileptogenesis

Starting date
March 1, 2017
Duration (months)
24
Departments
Neurosciences, Biomedicine and Movement Sciences
Managers or local contacts
Fabene Paolo

The problem: Safe, effective therapeutics to address refractory epilepsy and disease-modifying agents that
address the underlying disease process remain key unmet medical needs (Loscher, 2013). Current AEDs do
not cure epilepsy or treat the underlying pathology; rather, they reduce or block seizures, and are
ineffective for seizure control in up to 30% of patients. Serious and debilitating side effects (mood
disorders, ED, cognitive impairment, memory loss, social issues, ie restricted alcohol consumption etc) are
key issues for quality of life and compliance.
Our solution: We are hereby proposing a novel approach that targets not the neuron, but the other
components of the neurovascular unit, i.e. the leukocytes, leukocyte-vascular interactions (LVI), and
vascular integrity. Our data indicate that LVI and vascular leakage are major amplifying factors in seizure
and key therapeutic control points in the cascade of events contributing to seizures and epileptogenesis
and that this unique approach and our drug candidates are disease modifying agents (true antiepileptogenic)
that are also effective in treatment of refractory epilepsy. Notably, their mechanism of
action does not imply an alteration of the equilibrium in GABAergic tone, essential for cognitive tasks.
How?: We will focus on addressing the clear unmet medical need of blocking seizure in refractory epilepsy,
proposing here to investigate the mechanisms of actions (MOA), biomarkers, risk/benefit advantages and in
both refractory and prevention models as this integrated approach will maximize the power of the work
and results, better enabling future clinical trial design, patient selection and monitoring and therefore
success for both refractory patients and prevention scenarios. Prevention of epilepsy (eg following TBI) will
be thus the next target; the identification of biomarkers will allow to identify patients with the highest risk
of developing epilepsy.

Project participants

Paolo Fabene
Full Professor

Activities

Research facilities