Intranasal delivery of thyroid hormones in MCT8 deficiency
Publisher
Public Library of ScienceDate
2020-07-01Citation
10.1371/journal.pone.0236113
PLoS ONE 15.7 (2020): e0236113
ISSN
1932-6203DOI
10.1371/journal.pone.0236113Funded by
This work was supported by the Spanish Ministry of Economy and Competitiveness, grant number SAF2017-86342-R (MINECO/AEI/FEDER, UE) to AG-F, the Sherman Foundation (grant number OTR02211) to AG-F and SB-L, and the BBSRC (grant number BB/R016879/1) to SB-L. CG-M is a recipient of a contract from the Center for Biomedical Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid. S. R. was supported by grant DK15079 from the National Institutes of Health, USAProject
Gobierno de España. SAF2017-86342-REditor's Version
https://doi. org/10.1371/journal.pone.0236113Subjects
thyroid hormone; peripheral hyperthyroidism; brain hypothyroidism; therapeutic strategy; intranasal delivery route; MedicinaAbstract
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’-triiodo-thyronine (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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Google Scholar:Grijota-Martínez, Carmen
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Bárez-López, Soledad
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Ausó, Eva
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Refetoff, Samuel
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Frey, William H.
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Guadaño-Ferraz, Ana
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