The Role of mTOR Inhibitors in the Treatment of Patients with Tuberous Sclerosis Complex: Evidence-based and Expert Opinions

Paolo Curatolo, Marit Bjørnvold, Patricia E. Dill, José Carlos Ferreira, Martha Feucht, Christoph Hertzberg, Anna Jansen, Sergiusz Jóźwiak, J. Christopher Kingswood, Katarzyna Kotulska, Alfons Macaya, Romina Moavero, Rima Nabbout, Bernard A. Zonnenberg

Research output: Contribution to journalArticle

Abstract

Tuberous sclerosis complex (TSC) is a genetic disorder arising from mutations in the TSC1 or TSC2 genes. The resulting over-activation of the mammalian target of rapamycin (mTOR) signalling pathway leaves patients with TSC susceptible to the growth of non-malignant tumours in multiple organs. Previously, surgery was the main therapeutic option for TSC. However, pharmacological therapy with mTOR inhibitors such as everolimus and sirolimus is now emerging as an alternate approach. Everolimus and sirolimus have already been shown to be effective in treating subependymal giant cell astrocytoma (SEGA) and renal angiomyolipoma (AML), and everolimus is currently being evaluated in treating TSC-related epilepsy. In November 2013 a group of European experts convened to discuss the current options and practical considerations for treating various manifestations of TSC. This article provides evidence-based recommendations for the treatment of SEGA, TSC-related epilepsy and renal AML, with a focus on where mTOR inhibitor therapy may be considered alongside other treatment options. Safety considerations regarding mTOR inhibitor therapy are also reviewed. With evidence of beneficial effects in neurological and non-neurological TSC manifestations, mTOR inhibitors may represent a systemic treatment for TSC.

Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalDrugs
DOIs
Publication statusAccepted/In press - Feb 29 2016

    Fingerprint

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Curatolo, P., Bjørnvold, M., Dill, P. E., Ferreira, J. C., Feucht, M., Hertzberg, C., Jansen, A., Jóźwiak, S., Kingswood, J. C., Kotulska, K., Macaya, A., Moavero, R., Nabbout, R., & Zonnenberg, B. A. (Accepted/In press). The Role of mTOR Inhibitors in the Treatment of Patients with Tuberous Sclerosis Complex: Evidence-based and Expert Opinions. Drugs, 1-15. https://doi.org/10.1007/s40265-016-0552-9