Ingrid Scheffer is Chair of Pediatric Neurology at The University of Melbourne, Senior Principal Research Fellow at the Florey Institute of Neuroscience and Mental Health and the Murdoch Children's Research Institute. In addition to her remarkable national and international academic track record, Ingrid Scheffer serves as the President of the Australian Academy of Health and Medical Sciences. She has received many awards including the L'Oreal-UNESCO Warnen in Science Laureate, rarely awarded to a clinician-scientist, the Emil Becker Prize for outstanding contribution to paediatric neurology by the Gesellschaft Neuropädiatrie and an Officer of the Order of Australia. She was awarded the most prestigious science prize in Australia, the Prime Minister's Prize for Science, together with Prof Berkovic in 2014.
Developmental and epileptic encephalopathies (DEE) are among the most severe forms of epilepsy. DEEs are clinically and genetically heterogenous neurodevelopmental disorders characterized by multiple seizure types and developmental delay. Modern genetic advances have markedly accelerated the rate at which epilepsy genes have been identified, but in many children with DEE the cause remains unknown. Further questions remain, including the phenotypic spectrum of DEEs for a given genencluding associated comorbidities, genetic factors contributing to epilepsy onset and severity, and resistance to anti-seizure medication and targeted treatment approaches. Since individual DEEs are rare, international collaborations will allow us to tackle these critical questions.
In a joint research project, Samuel Berkovic and Ingrid Scheffer will implement a collaborative interdisciplinary approach to better define DEE phenotypes, to identify underlying genetic causes and disease mechanisms, and to identify novel DEE-targeted anti-seizure medication. Specifically, natural history studies will be implemented to expand the knowledge of the phenotypic spectrum of DEEs for a given gene and the genetic heterogeneity of specific epilepsy syndromes. They will identify genetic causes of DEEs and explore the role of somatic variants in epilepsy through cerebrospinal fluid liquid biopsies and/or brain sampling in patients undergoing epilepsy surgery. Mechanisms underlying DEEs will be investigated in cell and animal models using molecular, cell biological, immunohistological, imaging and electrophysiological approaches. We aim to identify anti-seizure medication targeting the underlying genetic cause from a precision medicine perspective. Berkovic and Scheffer expect that their results will contribute to our understanding of epileptogenesis and to new targeted treatment approaches.