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: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
06 January 2025
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| 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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| 245 | 1 | 0 | |a 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 |b study protocol |c 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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| 520 | |a 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. | ||
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