title: The Role of mTOR Inhibitors in the Treatment of Patients with Tuberous Sclerosis Complex: Evidence-based and Expert Opinions.
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.
authors.affiliation: Department of Neurosciences, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Rome, Italy. curatolo@uniroma2.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Curatolo
authors.affiliation: National Center for Rare Epilepsy-related Disorders, National Center of Epilepsy, Oslo University Hospital, Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Bjørnvold
authors.affiliation: Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital Basel, University of Basel, Basel, Switzerland.|INSERM Unité 1511, Paris, France.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Dill
authors.affiliation: Neuro Pediatra, Centro Hospitalar Lisboa Ocidental, Hospital São Francisco Xavier, Lisbon, Portugal.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Ferreira
authors.affiliation: Department of Paediatrics, University Hospital Vienna, Vienna, Austria.
authors.forename: Martha
authors.initials: M
authors.lastname: Feucht
authors.affiliation: Diagnose und Behandlungszentrum für Kinder und Jugendliche, Vivantes Klinikum Neukölln, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hertzberg
authors.affiliation: Pediatric Neurology Unit-UZ Brussel, Brussels, Belgium.
authors.forename: Anna
authors.initials: A
authors.lastname: Jansen
authors.affiliation: Department of Child Neurology, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Sergiusz
authors.initials: S
authors.lastname: Jóźwiak
authors.affiliation: Sussex Renal Unit, Royal Sussex County Hospital, Brighton, UK.|The Trafford Department of Renal Medicine, Royal Sussex County Hospital, Brighton, UK.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Kingswood
authors.affiliation: Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kotulska
authors.affiliation: Servei de Neurologia Pediàtrica, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Macaya
authors.affiliation: Department of Neurosciences, Child Neurology and Psychiatry Unit, Tor Vergata University Hospital of Rome, Rome, Italy.|Pediatric Neurology Unit, Department of Neuroscience and Neurorehabilitation, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Moavero
authors.affiliation: Department of Pediatric Neurology, Reference Centre for Rare Epilepsies and Tuberous Sclerosis Complex, Necker-Enfants Malades Hospital, University Paris Descartes, Paris, France.
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.affiliation: University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Zonnenberg
mesh_terms: D018207:Angiomyolipoma / Q000188:drug therapy; D001254:Astrocytoma / Q000188:drug therapy; D004827:Epilepsy / Q000188:drug therapy; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014402:Tuberous Sclerosis / Q000188:drug therapy*
chemical_list: D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases