Novel pharmacotherapies for the treatment of central hypothyroidism associated with Mct8/Oatp1c1 deficiency (P05)

• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 424957847

This project aims to develop peptide-T3 chimeras that enhance central T3 delivery, mitigating metabolic and behavioral disruptions linked to central T3 deficiency in the Mct8/Oatp1c1-deficient AHDS mouse model. In the previous funding period, first drugs promoting T3 transport across the blood-brain barrier have been developed and were shown to considerably improve T3 delivery and gene expression in mouse brains. However, T3 level enhancement remained suboptimal. In the next funding period, extended treatment effects will be evaluated and advanced chimeras designed. To this aim, assessments include impact on cognitive behavior, neurological phenotype and single nucleus RNA sequencing, and will further focus on delineating the optimum time of treatment, i.e. in utero vs. post-partum.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 296: Local control of TH action (LocoTact)
• Applicant Institution: Universität Duisburg-Essen
• Project Heads: Privatdozent Dr. Timo Müller; Professor Dr. Paul Pfluger