mTOR inhibitors as a new therapeutic option for epilepsy

Abstract

Dysregulation of the mTOR signaling pathway is associated with highly epileptogenic conditions such as tuberous sclerosis, focal cortical dysplasia, hemimegalencephaly and ganglioglioma, grouped under the term of ‘mTORopathies’. Brain abnormalities associated with mTOR overactivation include enlarged and dysplastic neurons, abnormal cortical organization and astrogliosis. mTOR signaling intervenes in several molecular/biochemical processes leading to epileptogenesis. Animal models demonstrated that mTOR inhibitors could exert both an anticonvulsant action and an antiepileptogenic effect in models of genetic and acquired epilepsy. Preliminary studies in patients affected by tuberous sclerosis and treated with rapamycin or everolimus demonstrated potential benefits in seizure frequency reduction, suggesting that mTOR inhibition could be a promising treatment option for mTORopathies-related epilepsy. The authors reviewed the current knowledge of mTOR overactivation in different forms of epilepsy, and discuss the potential clinical use of mTOR inhibitors.

Keywords::

• epilepsy
• epileptogenesis
• everolimus
• focal cortical dysplasia
• infantile spasms
• mTOR inhibitors
• phosphatase and tensin homolog
• rapamycin
• tuberous sclerosis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.