ESPE Abstracts

Thyroid hormone (TH) transporters are mandatory for proper TH metabolism and action as they facilitate the transmembrane passage of both T4 and T3. Inactivating mutations in the highly specific TH transporter MCT8 (encoded by the X-linked SLC16A2 gene) lead to severe intellectual and motor disabilities presumably due to a strongly diminished TH transport into the CNS and, consequently, an impaired neural development (Allan-Herndon-Dudley Syndrome, AHDS). Apart from a central TH deficiency, AHDS patients exhibit strongly altered TH parameters. In particular, highly elevated serum T3 concentrations causes a thyrotoxic state in peripheral organs thereby affecting e.g. liver, heart, kidney and skeletal muscle function. Different AHDS mouse models have been developed and revealed distinct cell- and organ-specific functions of Mct8 in mediating TH uptake and efflux. Moreover, AHDS mice were successfully exploited to test therapeutic strategies including the application of TH analogs, chaperone treatment and novel gene therapy approaches. In my presentation, I will summarize recent preclinical findings that eventually will pave the ground for an effective treatment strategy for this rare and devastating disease.