TY - JOUR
T1 - Molecular EPISTOP, a comprehensive multi-omic analysis of blood from Tuberous Sclerosis Complex infants age birth to two years
AU - Huschner, Franz
AU - Głowacka-Walas, Jagoda
AU - Mills, James D.
AU - Klonowska, Katarzyna
AU - Lasseter, Kathryn
AU - Asara, John M.
AU - Moavero, Romina
AU - Hertzberg, Christoph
AU - Weschke, Bernhard
AU - Riney, Kate
AU - Feucht, Martha
AU - Scholl, Theresa
AU - Krsek, Pavel
AU - Nabbout, Rima
AU - Jansen, Anna C.
AU - Petrák, Bořivoj
AU - van Scheppingen, Jackelien
AU - Zamecnik, Josef
AU - Iyer, Anand
AU - Anink, Jasper J.
AU - Mühlebner, Angelika
AU - Mijnsbergen, Caroline
AU - Lagae, Lieven
AU - Curatolo, Paolo
AU - Borkowska, Julita
AU - Sadowski, Krzysztof
AU - Domańska-Pakieła, Dorota
AU - Blazejczyk, Magdalena
AU - Jansen, Floor E.
AU - Janson, Stef
AU - Urbanska, Malgorzata
AU - Tempes, Aleksandra
AU - Janssen, Bart
AU - Sijko, Kamil
AU - Wojdan, Konrad
AU - Jozwiak, Sergiusz
AU - Kotulska, Katarzyna
AU - Lehmann, Karola
AU - Aronica, Eleonora
AU - Jaworski, Jacek
AU - Kwiatkowski, David J.
N1 - Funding Information: The authors wish to thank all of the numerous support personnel who enabled enrollment of subjects, collection of samples, etc. for EPISTOP, and the infants and parents who participated in EPISTOP. EPISTOP was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013; EPISTOP, grant agreement no. 602391, SJ), the Tuberous Sclerosis Alliance (no. 02-13, DJK), and Polish Ministerial funds for science (years 2013-2019). Publisher Copyright: © 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85177770701&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-023-42855-6
DO - https://doi.org/10.1038/s41467-023-42855-6
M3 - Article
C2 - 37996417
SN - 2041-1723
VL - 14
SP - 7664
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 7664
ER -