Radharani Benvenutti, Royal College of Surgeons in Ireland
€32.509 over 2 years
About the Project
Dravet syndrome is a severe treatment-resistant epileptic encephalopathy, characterized by prolonged seizures starting in infant's first years of life. Sudden Unexpected Death in Epilepsy (SUDEP) represents 53-61% of the deaths in Dravet syndrome. Nocturnal seizures, an important risk factor for SUDEP and a feature in patients with Dravet syndrome, are linked to severe sleep disturbances. Sleep disturbances are associated with the disruption of circadian rhythms, the body’s internal clock.
Despite efforts, no genetic, biochemical, or circadian signatures have yet been identified for this condition, and the urgent need for interventions to prevent SUDEP in Dravet syndrome remains. This research aims to identify circadian molecular biomarkers for Dravet pathogenesis and relevant SUDEP-linked phenotypes to, ultimately, predict SUDEP. The study will comprehensively characterize phenotypic and molecular signatures in a mouse model of Dravet Syndrome, to identify relevant biomarkers of disease progression and/or SUDEP risk. Following this, the study will seek to recruit Dravet syndrome patients across multiple clinical sites in Ireland to investigate their circadian rhythm profile by actigraphy and electroencephalography (EEG) assessments.
The final part of this project will seek to validate the pre-clinical biomarker findings in plasma samples from DS patients to assess its translational potential, while combining circadian clinical datasets.
It is hoped that this research will have a significant impact in potentially preventing SUDEP amongst patients with Dravet Syndrome.