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Intranasal delivery of Thyroid hormones in MCT8 deficiency
Loss of function mutations in the gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to severe neurodevelopmental defects in humans associated with a specific thyroid hormone phenotype manifesting high serum 3,5,3’-triiodothyronine (T3) and low thyroxine (T4) lev...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371167/ https://www.ncbi.nlm.nih.gov/pubmed/32687511 http://dx.doi.org/10.1371/journal.pone.0236113 |
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author | Grijota-Martínez, Carmen Bárez-López, Soledad Ausó, Eva Refetoff, Samuel Frey, William H. Guadaño-Ferraz, Ana |
author_facet | Grijota-Martínez, Carmen Bárez-López, Soledad Ausó, Eva Refetoff, Samuel Frey, William H. Guadaño-Ferraz, Ana |
author_sort | Grijota-Martínez, Carmen |
collection | PubMed |
description | Loss of function mutations in the gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to severe neurodevelopmental defects in humans associated with a specific thyroid hormone phenotype manifesting high serum 3,5,3’-triiodothyronine (T3) and low thyroxine (T4) levels. Patients present a paradoxical state of peripheral hyperthyroidism and brain hypothyroidism, this last one most likely arising from impaired thyroid hormone transport across the brain barriers. The administration of thyroid hormones by delivery pathways that bypass the brain barriers, such as the intranasal delivery route, offers the possibility to improve the neurological defects of MCT8-deficient patients. In this study, the thyroid hormones T4 and T3 were administrated intranasally in different mouse models of MCT8 deficiency. We have found that, under the present formulation, intranasal administration of thyroid hormones does not increase the content of thyroid hormones in the brain and further raises the peripheral thyroid hormone levels. Our data suggests intranasal delivery of thyroid hormones is not a suitable therapeutic strategy for MCT8 deficiency, although alternative formulations could be considered in the future to improve the nose-to-brain transport. |
format | Online Article Text |
id | pubmed-7371167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-73711672020-07-29 Intranasal delivery of Thyroid hormones in MCT8 deficiency Grijota-Martínez, Carmen Bárez-López, Soledad Ausó, Eva Refetoff, Samuel Frey, William H. Guadaño-Ferraz, Ana PLoS One Research Article Loss of function mutations in the gene encoding the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to severe neurodevelopmental defects in humans associated with a specific thyroid hormone phenotype manifesting high serum 3,5,3’-triiodothyronine (T3) and low thyroxine (T4) levels. Patients present a paradoxical state of peripheral hyperthyroidism and brain hypothyroidism, this last one most likely arising from impaired thyroid hormone transport across the brain barriers. The administration of thyroid hormones by delivery pathways that bypass the brain barriers, such as the intranasal delivery route, offers the possibility to improve the neurological defects of MCT8-deficient patients. In this study, the thyroid hormones T4 and T3 were administrated intranasally in different mouse models of MCT8 deficiency. We have found that, under the present formulation, intranasal administration of thyroid hormones does not increase the content of thyroid hormones in the brain and further raises the peripheral thyroid hormone levels. Our data suggests intranasal delivery of thyroid hormones is not a suitable therapeutic strategy for MCT8 deficiency, although alternative formulations could be considered in the future to improve the nose-to-brain transport. Public Library of Science 2020-07-20 /pmc/articles/PMC7371167/ /pubmed/32687511 http://dx.doi.org/10.1371/journal.pone.0236113 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Grijota-Martínez, Carmen Bárez-López, Soledad Ausó, Eva Refetoff, Samuel Frey, William H. Guadaño-Ferraz, Ana Intranasal delivery of Thyroid hormones in MCT8 deficiency |
title | Intranasal delivery of Thyroid hormones in MCT8 deficiency |
title_full | Intranasal delivery of Thyroid hormones in MCT8 deficiency |
title_fullStr | Intranasal delivery of Thyroid hormones in MCT8 deficiency |
title_full_unstemmed | Intranasal delivery of Thyroid hormones in MCT8 deficiency |
title_short | Intranasal delivery of Thyroid hormones in MCT8 deficiency |
title_sort | intranasal delivery of thyroid hormones in mct8 deficiency |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371167/ https://www.ncbi.nlm.nih.gov/pubmed/32687511 http://dx.doi.org/10.1371/journal.pone.0236113 |
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