Nature Communications (Nov 2023)
Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years
- Franz Huschner,
- Jagoda Głowacka-Walas,
- James D. Mills,
- Katarzyna Klonowska,
- Kathryn Lasseter,
- John M. Asara,
- Romina Moavero,
- Christoph Hertzberg,
- Bernhard Weschke,
- Kate Riney,
- Martha Feucht,
- Theresa Scholl,
- Pavel Krsek,
- Rima Nabbout,
- Anna C. Jansen,
- Bořivoj Petrák,
- Jackelien van Scheppingen,
- Josef Zamecnik,
- Anand Iyer,
- Jasper J. Anink,
- Angelika Mühlebner,
- Caroline Mijnsbergen,
- Lieven Lagae,
- Paolo Curatolo,
- Julita Borkowska,
- Krzysztof Sadowski,
- Dorota Domańska-Pakieła,
- Magdalena Blazejczyk,
- Floor E. Jansen,
- Stef Janson,
- Malgorzata Urbanska,
- Aleksandra Tempes,
- Bart Janssen,
- Kamil Sijko,
- Konrad Wojdan,
- Sergiusz Jozwiak,
- Katarzyna Kotulska,
- Karola Lehmann,
- Eleonora Aronica,
- Jacek Jaworski,
- David J. Kwiatkowski
Affiliations
- Franz Huschner
- Proteome Factory AG
- Jagoda Głowacka-Walas
- Transition Technologies Science
- James D. Mills
- Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
- Katarzyna Klonowska
- Department of Medicine, Brigham and Women’s Hospital
- Kathryn Lasseter
- Department of Medicine, Brigham and Women’s Hospital
- John M. Asara
- Department of Medicine, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center
- Romina Moavero
- Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University
- Christoph Hertzberg
- Diagnose- und Behandlungszentrum für Kinder, Vivantes-Klinikum Neukölln
- Bernhard Weschke
- Department of Child Neurology, Charité University Medicine Berlin
- Kate Riney
- Neurosciences Unit, Queensland Children’s Hospital
- Martha Feucht
- Epilepsy Service, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Member of ERN EpiCARE
- Theresa Scholl
- Epilepsy Service, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Member of ERN EpiCARE
- Pavel Krsek
- Department of Paediatric Neurology, Motol University Hospital, 2nd Medical Faculty, Charles University
- Rima Nabbout
- Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Necker–Enfants Malades Hospital, Université Paris cité, Imagine Institute
- Anna C. Jansen
- Neurogenetics Research Group, Vrije Universiteit Brussel
- Bořivoj Petrák
- Department of Paediatric Neurology, Motol University Hospital, 2nd Medical Faculty, Charles University
- Jackelien van Scheppingen
- Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
- Josef Zamecnik
- Department. of Pathology and Molecular Medicine, Motol University Hospital, 2nd Medical Faculty, Charles University
- Anand Iyer
- Department of Internal Medicine
- Jasper J. Anink
- Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
- Angelika Mühlebner
- Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
- Caroline Mijnsbergen
- Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
- Lieven Lagae
- Department of Development and Regeneration Section Pediatric Neurology, University Hospitals KU Leuven
- Paolo Curatolo
- Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University
- Julita Borkowska
- Department of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health Institute
- Krzysztof Sadowski
- Department of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health Institute
- Dorota Domańska-Pakieła
- Department of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health Institute
- Magdalena Blazejczyk
- Department of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health Institute
- Floor E. Jansen
- Department of Child Neurology, Brain Center University Medical Center Utrecht
- Stef Janson
- GenomeScan
- Malgorzata Urbanska
- Department of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health Institute
- Aleksandra Tempes
- International Institute of Molecular and Cell Biology
- Bart Janssen
- GenomeScan
- Kamil Sijko
- Transition Technologies Science
- Konrad Wojdan
- Transition Technologies Science
- Sergiusz Jozwiak
- Department of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health Institute
- Katarzyna Kotulska
- Department of Neurology and Epileptology, member of ERN EPICARE, The Children’s Memorial Health Institute
- Karola Lehmann
- Proteome Factory AG
- Eleonora Aronica
- Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience
- Jacek Jaworski
- International Institute of Molecular and Cell Biology
- David J. Kwiatkowski
- Department of Medicine, Brigham and Women’s Hospital
- DOI
- https://doi.org/10.1038/s41467-023-42855-6
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 15
Abstract
Abstract We present a comprehensive multi-omic analysis of the EPISTOP prospective clinical trial of early intervention with vigabatrin for pre-symptomatic epilepsy treatment in Tuberous Sclerosis Complex (TSC), in which 93 infants with TSC were followed from birth to age 2 years, seeking biomarkers of epilepsy development. Vigabatrin had profound effects on many metabolites, increasing serum deoxycytidine monophosphate (dCMP) levels 52-fold. Most serum proteins and metabolites, and blood RNA species showed significant change with age. Thirty-nine proteins, metabolites, and genes showed significant differences between age-matched control and TSC infants. Six also showed a progressive difference in expression between control, TSC without epilepsy, and TSC with epilepsy groups. A multivariate approach using enrollment samples identified multiple 3-variable predictors of epilepsy, with the best having a positive predictive value of 0.987. This rich dataset will enable further discovery and analysis of developmental effects, and associations with seizure development in TSC.
