The mTOR pathway as a therapeutic target for precision medicine

  • Patricia E. DillEmail author
  • Alexandre N. Datta


The mTOR-pathway (mTOR: mammalian target of rapamycin) has been increasingly linked to the pathophysiology of epilepsy in recent years. As a master regulator of cell growth and survival, this signaling pathway has been associated with focal malformations of cortical development (MCD) subtypes often associated with intractable epilepsy. The tuberous sclerosis complex serves as a model disease, in which targeted therapy with mTOR inhibitors alleviate, improve, and might even reverse disease burden. Further, there is evidence of an mTOR effect on established antiepileptic strategies such as ketogenic diet and GABAergic-enhancing medication, which underlies the importance of the mTOR pathway in epileptogenesis.


Signal pathways Epilepsy Tuberous sclerosis complex Focal cortical dysplasia Epileptogenesis 



Eukaryotic translation initiation factor 4E (elF4E)-binding protein 1


Adverse events


Protein kinase B




Autophagy-related protein 13




Focal cortical dysplasia


γ-Aminobutyric acid


Guanosine diphosphate


Glial fibrillary acidic protein


Glutamate aspartate transporter 1


Glutamate transporter 1






Ketogenic diet




Malformation of cortical development


Mammalian target of rapamycin


mTOR complex 1


mTOR complex 2


mTOR inhibitors


Phosphoinositide-dependent kinase-1


Phosphoinositide 3‑kinase


RAS homolog enriched in brain


70-kDa Ribosomal protein S6 kinase 1


Giant cell astrocytoma


Unc-51-like autophagy activating kinase 1



Der mTOR-Signalweg als therapeutisches Target für die Präzisionsmedizin


Der mTOR-Signalweg (mTOR: „mammalian target of rapamycin“) wird in den letzten Jahren zunehmend mit der Pathophysiologie der Epilepsie in Zusammenhang gebracht. Als einer der Hauptschnittpunkte in der Regulation von Zellwachstum und Überleben ist dieser Signalweg mit Subtypen fokaler Malformationen der kortikalen Entwicklung (MCD) vergesellschaftet, welche oft mit therapieresistenter Epilepsie einhergehen. Die tuberöse Sklerose dient hier als Modellerkrankung, bei welcher mit dem gezielten Einsatz von mTOR-Inhibitoren die Krankheitslast gelindert oder gar rückgängig gemacht werden kann. Darüber hinaus gibt es zunehmend Hinweise für einen mTOR-Effekt auf bereits etablierte antiepileptische Therapien wie ketogene Diät und GABAerg wirkende Substanzen, was die Wichtigkeit des mTOR-Signalwegs in der Epileptogenese unterstreicht.


Signalwege Epilepsie Tuberöse Sklerose Fokale kortikale Dysplasie Epileptogenese 


Compliance with ethical guidelines

Conflict of interest

P.E. Dill reports research grants, speaker honoraria and personal fees for advisory boards from Novartis. A.N. Datta has consultancy contracts with Idorsia Pharmaceuticals Ltd and F.Hoffmann-La Roche AG

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.


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Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pediatric Neurology and Developmental MedicineUniversity of Basel Children’s HospitalBaselSwitzerland

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