Engineering Nanocarriers for the Treatment of Allan-Herndon-Dudley Syndrome: Overcoming MCT8 Transport Deficiency

Children born with Allan-Herndon-Dudley Syndrome (AHDS) face severe neurodevelopmental challenges because they cannot properly transport an essential thyroid hormone called T3 to the brain. This happens because they have a defective "doorway" (called MCT8) that normally allows this hormone to enter the brain effectively. Without enough T3, the brain cannot develop and function properly, leading to significant disabilities. Currently, there is no effective treatment for these children, although a therapy involving T3 analog drugs is under experimental evaluation. Our research aims to create a new method to deliver this vital hormone to the brain without the need for a new drug by developing tiny carriers (called nanoparticles) that can bypass the defective doorway and transport physiological T3. Think of these nanoparticles as special transporters that can find alternative pathways to enter the brain. We will design these transporters with special "keys" (molecules called Angiopep-2-like peptides) that can unlock other doorways to the brain. Using advanced computational technologies, we will identify the most effective "keys" and create safe, biodegradable packages capable of carrying and releasing the hormone exactly where it is needed. If successful, this research could provide the first effective treatment for children with AHDS, offering real hope to families affected by this severe disability condition.