Role of mTOR inhibitors in epilepsy treatment

In spite of the fact, that subsequent new antiepileptic drugs (AEDs) are being introduced into clinical practice, the percentage of drug-resistant epilepsy cases remains stable. Although a substantial progress has been made in safety profile of antiepileptic drugs, currently available substances hav...

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Bibliographic Details
Published in:Pharmacological reports 2015-06, Vol.67 (3), p.636-646
Main Authors: Sadowski, Krzysztof, Kotulska-Jóźwiak, Katarzyna, Jóźwiak, Sergiusz
Format: Article
Language:English
Subjects:
Animals
Anticonvulsants - pharmacology
Anticonvulsants - therapeutic use
Brain - drug effects
Brain - metabolism
Drug Safety and Pharmacovigilance
Epilepsy
Epilepsy - drug therapy
Epilepsy - metabolism
Epileptogenesis
Humans
mTOR inhibitors
Pharmacotherapy
Pharmacy
Rapamycin
Review Article
Signal Transduction - drug effects
Signal Transduction - physiology
TOR Serine-Threonine Kinases - antagonists & inhibitors
TOR Serine-Threonine Kinases - metabolism
Treatment Outcome
Tuberous sclerosis
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Summary:In spite of the fact, that subsequent new antiepileptic drugs (AEDs) are being introduced into clinical practice, the percentage of drug-resistant epilepsy cases remains stable. Although a substantial progress has been made in safety profile of antiepileptic drugs, currently available substances have not been unambiguously proven to display disease-modifying effect in epilepsy and their mechanisms of action influence mainly on the end-stage phase of epileptogenesis, namely seizures. Prevention of epileptogenesis requires new generation of drugs modulating molecular pathways engaged in epileptogenesis processes. The mammalian target of rapamycin (mTOR) pathway is involved in highly epileptogenic conditions, such as tuberous sclerosis complex (TSC) and represents a reasonable target for antiepileptogenic interventions. In animal models of TSC mTOR inhibitors turned out to prevent the development of epilepsy and reduce underlying brain abnormalities. Accumulating evidence from animal studies suggest the role of mTOR pathway in acquired forms of epilepsy. Preliminary clinical studies with patients affected by TSC demonstrated seizure reduction and potential disease-modifying effect of mTOR inhibitors. Further studies will determine the place for mTOR inhibitors in the treatment of patients with TSC as well as its potential antiepileptogenic effect in other types of genetic and acquired epilepsies. This review presents current knowledge of mTOR pathway physiology and pathology in the brain, as well as potential clinical use of its inhibitors.
ISSN:1734-1140
2299-5684
DOI:10.1016/j.pharep.2014.12.017