A critical review of mTOR inhibitors and epilepsy: from basic science to clinical trials. (June 2013)

• Record Type: Journal Article
• Authors: Wong, Michael
• Is Part Of: Expert review of neurotherapeutics. Volume 13:Number 6(2013)
• Page Start: 657
• Page End: 669
• Publication Date: 2013-06
• Subjects: epilepsy -- epileptogenesis -- everolimus -- mTOR -- rapamycin -- seizures -- traumatic brain injury -- tuberous sclerosis; Neuropharmacology -- Periodicals; 615.7805
• DOI: 10.1586/ern.13.48
• Languages: English
• ISSNs: 1473-7175

Abstract

Present medications for epilepsy have substantial limitations, such as medical intractability in many patients and lack of antiepileptogenic properties to prevent epilepsy. Drugs with novel mechanisms of action are needed to overcome these limitations. The mTOR signaling pathway has emerged as a possible therapeutic target for epilepsy. Preliminary clinical trials suggest that mTOR inhibitors reduce seizures in tuberous sclerosis complex (TSC) patients with intractable epilepsy. Furthermore, mTOR inhibitors have antiepileptogenic properties in preventing epilepsy in animal models of TSC. Besides TSC, accumulating preclinical data suggest that mTOR inhibitors may have antiseizure or antiepileptogenic actions in other types of epilepsy, including infantile spasms, neonatal hypoxic seizures, absence epilepsy and acquired temporal lobe epilepsy following brain injury, but these effects depend on a number of conditions. Future clinical and basic research is needed to establish whether mTOR inhibitors are an effective treatment for epilepsy.