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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...

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Main Authors: Driedger, Jan Henje (Author) , Schröter, Julian (Author) , Hertzberg, Christoph (Author) , Weschke, Bernhard (Author) , Kaindl, Angela M. (Author) , Lücke, Thomas (Author) , Thiels, Charlotte (Author) , Klotz, Kerstin A. (Author) , Fazeli, Walid (Author) , Rostásy, Kevin (Author) , Wiethoff-Ubrig, Lucia (Author) , Kaiser, Olaf (Author) , Trollmann, Regina (Author) , Mammadova, Dilbar (Author) , Schubert-Bast, Susanne (Author) , Bach, Alexia (Author) , Eckenweiler, Matthias (Author) , Schönberger, Jan (Author) , Martakis, Kyriakos (Author) , Hahn, Andreas (Author) , Brockmann, Knut (Author) , Dreha-Kulaczewski, Steffi (Author) , Weiss, Deike (Author) , Denecke, Jonas (Author) , Muhle, Hiltrud (Author) , Arélin, Maria (Author) , Merkenschlager, Andreas (Author) , Borggräfe, Ingo (Author) , Roser, Timo (Author) , Ebrahimi-Fakhari, Daniel (Author) , Fiedler, Barbara (Author) , Schlump, Jan-Ulrich (Author) , Köster, Ilka (Author) , Korenke, Christoph (Author) , Alber, Michael (Author) , Ruf, Susanne (Author) , Feucht, Martha (Author) , Scholl, Theresa (Author) , Syrbe, Steffen (Author) , Saffari, Afshin (Author)
Format: Article (Journal)
Language:English
Published: 06 January 2025
In: Orphanet journal of rare diseases
Year: 2025, Volume: 20, Pages: 1-10
ISSN:1750-1172
DOI:10.1186/s13023-024-03495-1
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1186/s13023-024-03495-1
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Author Notes: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
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Summary: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.
Item Description:Gesehen am 14.03.2025
Physical Description:Online Resource
ISSN:1750-1172
DOI:10.1186/s13023-024-03495-1

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