Journal
PLOS ONE
Volume 15, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0236113
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Funding
- Spanish Ministry of Economy and Competitiveness (MINECO/AEI/FEDER, UE) [SAF2017-86342-R]
- Sherman Foundation [OTR02211]
- BBSRC [BB/R016879/1]
- National Institutes of Health, USA [DK15079]
- FEDER funds (European Funds for Regional Development)
- CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI)
- BBSRC [BB/R016879/1] Funding Source: UKRI
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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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