Pharmacological stimulation of mitochondrial metabolism as a therapeutic approach in a mouse model of AHDS
- NaN
Allan-Herndon-Dudley syndrome (AHDS) is a rare disorder of brain development that causes severe intellectual disability and problems with movement. Affected children are wheelchair users and have impaired speech and limited ability to communicate. Mutations in the SLC16A2 gene cause AHDS. This gene provides instructions for making a protein called MCT8, a transporter for thyroid hormone (T3) in the brain. The symptoms of the disease are due to the inability of T3 to reach the developing brain, and they appear a few months after birth. To date, there are no effective treatments for AHDS.
The T3 hormone regulates energy production within the brain's cells through the activation of important chemical reactions called metabolism, which mainly occur inside organelles named mitochondria. We have produced test-tube brain models called organoids, and we have observed that, without T3, organoids substantially alter their metabolism, and consequently, neurons do not develop properly. However, a drug called Nicotinamide Riboside (NR), which activates cellular metabolism and mitochondrial function, favoured the organoids' maturation, even without T3. This project aims to test a novel therapeutic strategy to promote neuronal development in AHDS. To achieve this, we will confirm the efficacy of NR in an animal model of AHDS by administering NR from the foetal stage. This project will provide essential advances in therapeutic options for AHDS.
