Sam Berkovic is Laureate Professor in the Department of Medicine at The University of Melbourne and Director of the Epilepsy Research Centre at Austin Health in Australia. His work has been recognized by numerous prizes including election to the Royal Society (London) and as an international member of the National Academy of Medicine (USA). In 2014, he was appointed as a Companion of the Order of Australia for his eminent service to biomedical research in the field of epilepsy genetics, to the study of neurology on a national and international level, and for his work as an ambassador for medical science education in Australia.
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. The aim is 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.