WONOEP appraisal: Modeling early onset epilepsies.

Autor: De Meulemeester AS; Institut du Cerveau-Paris Brain Institute-ICM, Institut National de la Santé et de la Recherche Médicale (INSERM), CNRS, Sorbonne Université, Paris, France.; Laboratory for Molecular Biodiscovery, KU Leuven, Leuven, Belgium., Reid C; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.; Department of Medicine, Epilepsy Research Centre, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia., Auvin S; Pediatric Neurology Department, CRMR Épilepsies Rares, EpiCARE member, AP-HP, Robert-Debré University Hospital, Paris, France.; INSERM NeuroDiderot, Université Paris Cité, Paris, France.; Institut Universitaire de France, Paris, France., Carlen PL; Krembil Research Institute, Toronto, Ontario, Canada.; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.; Department of Medicine and Physiology, University of Toronto, Toronto, Ontario, Canada., Cole AJ; MGH Epilepsy Service, Division of Clinical Neurophysiology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA., Szlendak R; Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland.; Institut de Génomique Fonctionnelle, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Montpellier, France., Di Sapia R; Department of Acute Brain and Cardiovascular Injury, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy., Moshé SL; Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.; Isabelle Rapin Division of Child Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.; Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York, USA., Sankar R; Department of Neurology and Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA., O'Brien TJ; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.; Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.; Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia., Baulac S; Institut du Cerveau-Paris Brain Institute-ICM, Institut National de la Santé et de la Recherche Médicale (INSERM), CNRS, Sorbonne Université, Paris, France., Henshall DC; FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland.; Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences, Dublin, Ireland., Akman Ö; Department of Physiology, Faculty of Medicine, Demiroglu Bilim University, Istanbul, Turkey., Galanopoulou AS; Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.; Isabelle Rapin Division of Child Neurology, Albert Einstein College of Medicine, Bronx, New York, USA.; Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2024 Jul 23. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1111/epi.18063
Abstrakt: Epilepsy has a peak incidence during the neonatal to early childhood period. These early onset epilepsies may be severe conditions frequently associated with comorbidities such as developmental deficits and intellectual disability and, in a significant percentage of patients, may be medication-resistant. The use of adult rodent models in the exploration of mechanisms and treatments for early life epilepsies is challenging, as it ignores significant age-specific developmental differences. More recently, models developed in immature animals, such as rodent pups, or in three-dimensional organoids may more closely model aspects of the immature brain and could result in more translatable findings. Although models are not perfect, they may offer a more controlled screening platform in studies of mechanisms and treatments, which cannot be done in pediatric patient cohorts. On the other hand, more simplified models with higher throughput capacities are required to deal with the large number of epilepsy candidate genes and the need for new treatment options. Therefore, a combination of different modeling approaches will be beneficial in addressing the unmet needs of pediatric epilepsy patients. In this review, we summarize the discussions on this topic that occurred during the XVI Workshop on Neurobiology of Epilepsy, organized in 2022 by the Neurobiology Commission of the International League Against Epilepsy. We provide an overview of selected models of early onset epilepsies, discussing their advantages and disadvantages. Heterologous expression models provide initial functional insights, and zebrafish, rodent models, and brain organoids present increasingly complex platforms for modeling and validating epilepsy-related phenomena. Together, these models offer valuable insights into early onset epilepsies and accelerate hypothesis generation and therapy discovery.
(© 2024 International League Against Epilepsy.)
Databáze: MEDLINE
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