Project R-14084

Creation of a humanized mouse model for Charcot Marie Tooth disease type 1A (Research)

Charcot-Marie-Tooth disease (CMT) affects 1 in 2500 individuals worldwide and is characterized by progressive damage to the peripheral motor and sensory nerves. The most prevalent disease form, CMT type 1A (CMT1A), is caused by a peripheral myelin protein 22 (PMP22) gene duplication. PMP22 is mainly expressed by Schwann cells, the myelinating cells of the peripheral nervous system. Despite preclinical successes, there is no cure for CMT1A, mainly due to the lack of translatable CMT1A disease models to study the disease. I will use human dental pulp stem cell-derived Schwann cells to develop a humanized mouse model for CMT1A. Using state-of-the-art non-invasive imaging techniques such as small-animal BLI, PET and MRI, I will monitor Schwann cell survival and persistence in vivo over time in the same animals. The model will be the first to recapitulate the disease, and therefore provide us with insights into the pathology. Furthermore, the humanized mouse model offers a novel and unique opportunity to validate candidate therapies for CMT1A.

01 October 2023 - 30 September 2024