Project R-13547

Creation of a humanized mouse model for demyelinating peripheral neuropathies as a platform for therapeutic testing. (Research)

Charcot-Marie-Tooth disease type 1 (CMT1) is a demyelinating peripheral neuropathy characterized by slowly progressing muscle weakness and the development of sensory problems. CMT1 is a genetic disease caused by mutations or copy number variations in several genes in Schwann cells, responsible for myelination. There is no cure for CMT because of an insufficient understanding of the pathogenesis. In this project, we start from stem cells and develop a humanized mouse model for CMT1. The model will recapitulate the disease, including the impact of inflammatory responses. We inject stem cell derived Schwann cells in the presence of a humanized immune system. We will also get better insights into the disease mechanism by using Schwann cells containing CMT1-causing genetic alterations. The humanized mouse model offers a novel and unique opportunity to validate candidate therapies for dominant and recessive forms of CMT1 and will contribute to a better understanding of CMT.

01 January 2023 - 31 December 2026