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Background <p>Tuberous sclerosis complex (TSC) is a&#xa0;rare genetic disorder characterized by constitutive mTOR overactivation, leading to early onset epilepsy as well as cognitive and neuropsychiatric disorders. Treatment strategies are currently shifting from symptomatic treatment towards preventive, potentially disease-modifying approaches.</p> Objective <p>We analyzed the current evidence for preventive treatment strategies in TSC, with a&#xa0;particular focus on the presymptomatic use of vigabatrin and mTOR inhibitors and discuss their impact on the epilepsy course and development.</p> Material and methods <p>A&#xa0;narrative synthesis of available preclinical and clinical data on preventive treatment in TSC was carried out, including an overview of ongoing clinical studies.</p> Results <p>There is evidence that presymptomatic vigabatrin treatment initiated in the presence of epileptiform electroencephalography (EEG) abnormalities delays seizure onset and reduces the risk of infantile spasms; however, a&#xa0;reproducible and consistent effect on cognitive development has not yet been demonstrated. For mTOR inhibitors, disease-modifying effects on neuronal architecture and behavior have been demonstrated in preclinical and animal models. Robust data on the long-term neurocognitive outcomes of presymptomatic treatment with sirolimus are still lacking. Intrauterine mTOR inhibition is currently reserved for selected cases with life-threatening cardiac manifestations as reliable neurological outcome data are not yet available.</p> Discussion <p>Preventive treatment in TSC has the potential to favorably influence the epileptogenesis. A&#xa0;clear benefit for neurocognitive development has not yet been confirmed. Ongoing controlled studies, such as the PROTECT study in Germany and Austria as well as trials in the USA and Poland, will be essential to define the role of presymptomatic mTOR inhibition as a&#xa0;disease-modifying strategy and to determine the optimal therapeutic time window.</p>

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Präventive Therapie bei tuberöser Sklerose: Konzepte, Evidenz und offene Fragen

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月17日

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  • Jan Henje Driedger,
  • Steffen Syrbe

摘要

Background

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by constitutive mTOR overactivation, leading to early onset epilepsy as well as cognitive and neuropsychiatric disorders. Treatment strategies are currently shifting from symptomatic treatment towards preventive, potentially disease-modifying approaches.

Objective

We analyzed the current evidence for preventive treatment strategies in TSC, with a particular focus on the presymptomatic use of vigabatrin and mTOR inhibitors and discuss their impact on the epilepsy course and development.

Material and methods

A narrative synthesis of available preclinical and clinical data on preventive treatment in TSC was carried out, including an overview of ongoing clinical studies.

Results

There is evidence that presymptomatic vigabatrin treatment initiated in the presence of epileptiform electroencephalography (EEG) abnormalities delays seizure onset and reduces the risk of infantile spasms; however, a reproducible and consistent effect on cognitive development has not yet been demonstrated. For mTOR inhibitors, disease-modifying effects on neuronal architecture and behavior have been demonstrated in preclinical and animal models. Robust data on the long-term neurocognitive outcomes of presymptomatic treatment with sirolimus are still lacking. Intrauterine mTOR inhibition is currently reserved for selected cases with life-threatening cardiac manifestations as reliable neurological outcome data are not yet available.

Discussion

Preventive treatment in TSC has the potential to favorably influence the epileptogenesis. A clear benefit for neurocognitive development has not yet been confirmed. Ongoing controlled studies, such as the PROTECT study in Germany and Austria as well as trials in the USA and Poland, will be essential to define the role of presymptomatic mTOR inhibition as a disease-modifying strategy and to determine the optimal therapeutic time window.