Cristina Reschke, PhD – RCSI University of Medicine and Health Sciences
DS-TIME: a multi-assessment approach to uncover the underlying mechanisms of sleep disturbances in children with Dravet syndrome
Clinical Research Grant – $250,000, 2 years
Grant Summary:
Dravet syndrome (DS) is a very difficult to treat epilepsy syndrome characterized by seizures that start in the first years of life. However, a number of other symptoms are extremely relevant due to an expressive negative impact on the quality of life of DS children and their families. Among these, most caregivers report concerns about sleep problems and highlight the urgent need for a better diagnosis and management of severe sleep disorders in DS children. Despite there is some scientific evidence linking sleep disturbances to a disruption of the circadian system, the underlying mechanisms of sleep disturbances in DS children are poorly characterized. The sleep is mainly regulated by our body’s rhythms, named as circadian rhythms. The circadian system determines the 24-hour cycles in body changes, which include the regulation of sleep patterns, hormones, body temperature, and brain waves. These biological rhythms are driven by a master clock in the brain, called the suprachiasmatic nucleus, which is responsible for regulating the release of a neuro hormone called melatonin. Importantly, melatonin exerts an essential role in regulating the sleep-wake cycles in response to people’s exposure to environmental light or dark. Studies have shown that abnormalities in the circadian control of the secretion of melatonin may represent an important role in sleep disorders, however, the circadian cycle pattern remains unknown in DS children. Furthermore, the precise molecular mechanisms of sleep disturbances in DS children are also poorly understood and there are no tools to predict the risk of developing severe sleep problems. In this project, we will primarily focus on characterizing sleep and circadian patterns in DS children and their families (siblings and caregivers), using multiple clinical and molecular assessments involving questionnaires, the use of a long-term actigraph device and multiple saliva collections. After, we will use several computational tools to identify and classify the severity of their sleep disturbances. Finally, we will link the clinical findings with the molecular findings to identify possible causes related to severe sleep disorders. The results obtained from this study will not only improve the understanding of sleep disorders in children with DS and its impact on their families but will also lay a crucial foundation for the future development of early diagnostic tools aimed at reducing these sleep disturbances in DS children.
About the Investigator:
Cristina R. Reschke is Lecturer in the School of Pharmacy and Biomolecular Sciences and Funded Investigator within FutureNeuro Research Centre at RCSI University of Medicine and Health Sciences, Ireland. She trained as Clinical Pharmacist and holds MSc and PhD in Pharmacology, which were focused on epilepsy treatment. Cristina’s major discoveries are on microRNA-based therapies and the pre-clinical development of novel oligonucleotide delivery systems. She received a number of international awards, including the Harinarayan and the Grass awards, endowed by the International League Against Epilepsy (ILAE) and the American Epilepsy Society, respectively. Cristina’s research focuses on uncovering cellular and molecular mechanisms underlying epilepsy to allow for the development of novel and precise therapeutic and diagnostic approaches. Specifically, she is interested in the chronobiology of epilepsy. Cristina serves in a number of ILAE task forces and is the past Global Treasurer for the Young Epilepsy Section (YES) of the ILAE (2021-2023). Nationally, she is the Academic member for the Irish Epilepsy League Council and the Academic Director for the RCSI International Citizenship Programme.
