Charcot-Marie-Tooth disease (CMT) is an inherited condition which causes damage to nerve cells known as motor neurons. These cells are important as they ‘communicate’ between the spinal cord and muscles, sending signals to make muscles contract. If they are damaged, this communication is broken, which causes muscles to weaken.
More than 90 different genes can cause CMT, leading to different types of CMT. This project will focus on one type, CMT2D, caused by changes in the GARS1 gene. Some potential treatments will soon be entering clinical trials; however, it is unknown whether genetic changes in GARS1 directly cause nerve cells to stop working or if the damage of nerve cells is caused indirectly through weakened muscles. This is important to understand, as the new therapies need to be designed to target the primary tissue responsible for the development of the condition.
The main aim of this project is to determine whether CMT2D is caused in the nerve or muscle tissue to help inform imminent clinical trials. This will be done using animal models, which the researchers aim to generate during the project, and then looking at different tissues in with and without the GARS1 gene.
Why this research is important
CMT is a common condition for which there is no treatment. A number of therapies currently being designed are nearing entry into clinical trials. Understanding the tissue where CMT is caused will allow for improved design of the therapies for CMT that are about to enter clinical trials.