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Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy

Tuberous sclerosis complex (TSC) is a relatively rare genetic disorder, affecting one in 6,000 births. Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, which have been previously used to prevent solid organ transplant rejection, augment anticancer treatment regimens, and prevent...

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Autores principales: Capal, Jamie K, Franz, David Neal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003595/
https://www.ncbi.nlm.nih.gov/pubmed/27601910
http://dx.doi.org/10.2147/NDT.S91248
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author Capal, Jamie K
Franz, David Neal
author_facet Capal, Jamie K
Franz, David Neal
author_sort Capal, Jamie K
collection PubMed
description Tuberous sclerosis complex (TSC) is a relatively rare genetic disorder, affecting one in 6,000 births. Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, which have been previously used to prevent solid organ transplant rejection, augment anticancer treatment regimens, and prevent neovascularization of artificial cardiac stents, are now approved for treating TSC-related manifestations, such as subependymal giant cell astrocytomas and renal angiomyolipomas. The use of everolimus in treating subependymal giant cell astrocytomas is supported by long-term Phase II and III clinical trials. Seizures are a common feature in TSC, occurring in up to 96% of patients. While mTOR inhibitors currently do not have regulatory approval in treating this manifestation, small clinical studies have demonstrated beneficial outcomes with everolimus. Further evidence from a forthcoming Phase III clinical study may provide additional support for the use of everolimus for this indication. Also, there are no approved treatments for TSC-associated neuropsychiatric disorders, which include intellectual disability, behavioral difficulties, and autism spectrum disorder, but preclinical data and small studies have suggested that some neuropsychiatric symptoms may be improved through mTOR inhibition therapy. More evidence is needed, particularly regarding safety in young infants. This review focuses on the current evidence supporting the use of everolimus in neurologic and neuropsychiatric manifestations of TSC, and the place of everolimus in therapy.
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spelling pubmed-50035952016-09-06 Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy Capal, Jamie K Franz, David Neal Neuropsychiatr Dis Treat Review Tuberous sclerosis complex (TSC) is a relatively rare genetic disorder, affecting one in 6,000 births. Mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, which have been previously used to prevent solid organ transplant rejection, augment anticancer treatment regimens, and prevent neovascularization of artificial cardiac stents, are now approved for treating TSC-related manifestations, such as subependymal giant cell astrocytomas and renal angiomyolipomas. The use of everolimus in treating subependymal giant cell astrocytomas is supported by long-term Phase II and III clinical trials. Seizures are a common feature in TSC, occurring in up to 96% of patients. While mTOR inhibitors currently do not have regulatory approval in treating this manifestation, small clinical studies have demonstrated beneficial outcomes with everolimus. Further evidence from a forthcoming Phase III clinical study may provide additional support for the use of everolimus for this indication. Also, there are no approved treatments for TSC-associated neuropsychiatric disorders, which include intellectual disability, behavioral difficulties, and autism spectrum disorder, but preclinical data and small studies have suggested that some neuropsychiatric symptoms may be improved through mTOR inhibition therapy. More evidence is needed, particularly regarding safety in young infants. This review focuses on the current evidence supporting the use of everolimus in neurologic and neuropsychiatric manifestations of TSC, and the place of everolimus in therapy. Dove Medical Press 2016-08-25 /pmc/articles/PMC5003595/ /pubmed/27601910 http://dx.doi.org/10.2147/NDT.S91248 Text en © 2016 Capal and Franz. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Review
Capal, Jamie K
Franz, David Neal
Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy
title Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy
title_full Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy
title_fullStr Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy
title_full_unstemmed Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy
title_short Profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy
title_sort profile of everolimus in the treatment of tuberous sclerosis complex: an evidence-based review of its place in therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5003595/
https://www.ncbi.nlm.nih.gov/pubmed/27601910
http://dx.doi.org/10.2147/NDT.S91248
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