Buchumschlag

Long-term neuropsychologic outcome of pre-emptive mTOR inhibitor treatment in children with tuberous sclerosis complex (TSC) under 4 months of age (PROTECT), a two-arm, randomized, observer-blind, controlled phase IIb national multicentre clinical trial: study protocol

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organ systems, with a prevalence of 1:6,760-1:13,520 live births in Germany. On the molecular level, TSC is caused by heterozygous loss-of-function variants in either of the genes TSC1 or TSC2, encoding the...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Driedger, Jan Henje (VerfasserIn) , Schröter, Julian (VerfasserIn) , Hertzberg, Christoph (VerfasserIn) , Weschke, Bernhard (VerfasserIn) , Kaindl, Angela M. (VerfasserIn) , Lücke, Thomas (VerfasserIn) , Thiels, Charlotte (VerfasserIn) , Klotz, Kerstin A. (VerfasserIn) , Fazeli, Walid (VerfasserIn) , Rostásy, Kevin (VerfasserIn) , Wiethoff-Ubrig, Lucia (VerfasserIn) , Kaiser, Olaf (VerfasserIn) , Trollmann, Regina (VerfasserIn) , Mammadova, Dilbar (VerfasserIn) , Schubert-Bast, Susanne (VerfasserIn) , Bach, Alexia (VerfasserIn) , Eckenweiler, Matthias (VerfasserIn) , Schönberger, Jan (VerfasserIn) , Martakis, Kyriakos (VerfasserIn) , Hahn, Andreas (VerfasserIn) , Brockmann, Knut (VerfasserIn) , Dreha-Kulaczewski, Steffi (VerfasserIn) , Weiss, Deike (VerfasserIn) , Denecke, Jonas (VerfasserIn) , Muhle, Hiltrud (VerfasserIn) , Arélin, Maria (VerfasserIn) , Merkenschlager, Andreas (VerfasserIn) , Borggräfe, Ingo (VerfasserIn) , Roser, Timo (VerfasserIn) , Ebrahimi-Fakhari, Daniel (VerfasserIn) , Fiedler, Barbara (VerfasserIn) , Schlump, Jan-Ulrich (VerfasserIn) , Köster, Ilka (VerfasserIn) , Korenke, Christoph (VerfasserIn) , Alber, Michael (VerfasserIn) , Ruf, Susanne (VerfasserIn) , Feucht, Martha (VerfasserIn) , Scholl, Theresa (VerfasserIn) , Syrbe, Steffen (VerfasserIn) , Saffari, Afshin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 06 January 2025
In: Orphanet journal of rare diseases
Year: 2025, Jahrgang: 20, Pages: 1-10
ISSN:1750-1172
DOI:10.1186/s13023-024-03495-1
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1186/s13023-024-03495-1
Volltext
Verfasserangaben:Jan H. Driedger, Julian Schröter, Christoph Hertzberg, Bernhard Weschke, Angela M. Kaindl, Thomas Lücke, Charlotte Thiels, Kerstin Alexandra Klotz, Walid Fazeli, Kevin Rostásy, Lucia Wiethoff-Ubrig, Olaf Kaiser, Regina Trollmann, Dilbar Mammadova, Susanne Schubert-Bast, Alexia Bach, Matthias Eckenweiler, Jan Schönberger, Kyriakos Martakis, Andreas Hahn, Knut Brockmann, Steffi Dreha-Kulaczewski, Deike Weiss, Jonas Denecke, Hiltrud Muhle, Maria Arelin, Andreas Merkenschlager, Ingo Borggräfe, Timo Roser, Daniel Ebrahimi-Fakhari, Barbara Fiedler, Jan-Ulrich Schlump, Ilka Köster, Christoph Korenke, Michael Alber, Susanne Ruf, Martha Feucht, Theresa Scholl, Steffen Syrbe, Afshin Saffari, PROTECT-Study Group
Beschreibung
Zusammenfassung:Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder affecting multiple organ systems, with a prevalence of 1:6,760-1:13,520 live births in Germany. On the molecular level, TSC is caused by heterozygous loss-of-function variants in either of the genes TSC1 or TSC2, encoding the Tuberin-Hamartin complex, which acts as a critical upstream suppressor of the mammalian target of rapamycin (mTOR), a key signaling pathway controlling cellular growth and metabolism. Despite the therapeutic success of mTOR inhibition in treating TSC-associated manifestations, studies with mTOR inhibitors in children with TSC above two years of age have failed to demonstrate beneficial effects on disease-related neuropsychological deficits. It has thus been hypothesized, that the critical time window for mTOR inhibitors may lie in early infancy, before TSC-related symptoms such as early-onset epilepsy and infantile spasms as sign of disruptive brain maturation occur. No controlled prospective clinical trials have evaluated the effect of pre-symptomatic mTOR inhibitor therapy on neuropsychological manifestations in TSC patients under two years of age.
Beschreibung:Gesehen am 14.03.2025
Beschreibung:Online Resource
ISSN:1750-1172
DOI:10.1186/s13023-024-03495-1

Ähnliche Einträge