ArticleJCI insight2024
Impaired T3 uptake and action in MCT8-deficient cerebral organoids underlie Allan-Herndon-Dudley syndrome.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Multiscale characterization and distribution of the thyroid hormone transporter MCT8 in the adult and aged human brain.Acta neuropathologica communications · 2026Article
- Article
- GluN2A-mediated currents and calcium signal in human iPSC-derived neurons.Scientific reports · 2026Article
- T3 enhances neuronal activity in an induced pluripotent stem cell derived model of early human brain development.European thyroid journal · 2026Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Thyroid hormone promotes fetal neurogenesis.JCI insight · 2025Article
- Maternal thyroid hormone is required to develop the hindbrain vasculature in zebrafish.Communications biology · 2025Article
- Patients with Allan-Herndon-Dudley Syndrome (MCT8 Deficiency) Display Symptoms of Parkinsonism in Childhood and Respond to Levodopa/Carbidopa Treatment.Movement disorders : official journal of the Movement Disorder Society · 2025Observational
- Variable transduction of thyroid hormone signaling in structures of the mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- NovelPharmacogenomics and personalized medicine · 2025Article
- Toward a treatment for thyroid hormone transporter MCT8 deficiency - achievements and challenges.European thyroid journal · 2024Review
- Mapping Thyroid Hormone Action in the Human Brain.Thyroid : official journal of the American Thyroid Association · 2024Review
- Spatiotemporal expression of thyroid hormone transporter MCT8 and THRA mRNA in human cerebral organoids recapitulating first trimester cortex development.Scientific reports · 2024Article
- Unmet patient needs in monocarboxylate transporter 8 (MCT8) deficiency: a review.Frontiers in pediatrics · 2024Review
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Authors and funding
5 authors at 1 institution in 2 countries.
Funding
Abstract
Patients with mutations in the thyroid hormone (TH) cell transporter monocarboxylate transporter 8 (MCT8) gene develop severe neuropsychomotor retardation known as Allan-Herndon-Dudley syndrome (AHDS). It is assumed that this is caused by a reduction in TH signaling in the developing brain during both intrauterine and postnatal developmental stages, and treatment remains understandably challenging. Given species differences in brain TH transporters and the limitations of studies in mice, we generated cerebral organoids (COs) using human induced pluripotent stem cells (iPSCs) from MCT8-deficient patients. MCT8-deficient COs exhibited (i) altered early neurodevelopment, resulting in smaller neural rosettes with thinner cortical units, (ii) impaired triiodothyronine (T3) transport in developing neural cells, as assessed through deiodinase-3-mediated T3 catabolism, (iii) reduced expression of genes involved in cerebral cortex development, and (iv) reduced T3 inducibility of TH-regulated genes. In contrast, the TH analogs 3,5-diiodothyropropionic acid and 3,3',5-triiodothyroacetic acid triggered normal responses (induction/repression of T3-responsive genes) in MCT8-deficient COs, constituting proof of concept that lack of T3 transport underlies the pathophysiology of AHDS and demonstrating the clinical potential for TH analogs to be used in treating patients with AHDS. MCT8-deficient COs represent a species-specific relevant preclinical model that can be utilized to screen drugs with potential benefits as personalized therapeutics for patients with AHDS.
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