RT Journal Article
T1 Intranasal delivery of thyroid hormones in MCT8 deficiency
A1 Grijota Martínez, María Carmen
A1 Bárez López, Soledad
A1 Ausó, Eva
A1 Refetoff, Samuel
A1 Frey, William H.
A1 Guadaño Ferraz, Ana
A2 Iglesias Osma, Maria Carmen
AB 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.
PB Public Library of Science
SN 1932-6203
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/92644
UL https://hdl.handle.net/20.500.14352/92644
LA eng
NO Grijota-Martínez C, Bárez-López S, Ausó E, Refetoff S, Frey WH II, Guadaño-Ferraz A (2020) Intranasal delivery of Thyroid hormones in MCT8 deficiency. PLoS ONE 15(7): e0236113. https://doi.org/10.1371/journal.pone.0236113
NO Ministerio de Economía y Competitividad (España)
NO Sherman Foundation
NO Biotechnology and Biological Sciences Research Council (UK)
NO Instituto de Salud Carlos III. 
NO National Institutes of Health (USA)
DS Docta Complutense
RD 28 abr 2025