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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...

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Autores principales: Grijota-Martínez, Carmen, Bárez-López, Soledad, Ausó, Eva, Refetoff, Samuel, Frey, William H., Guadaño-Ferraz, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
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.
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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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