Washington University in St. Louis (WU)
Charcot-Marie-Tooth (CMT) disease type 2A is an uncurable peripheral neuropathy disease caused by mutations in mitochondrial fusion protein, mitofusin2 (MFN2). Today, ~100 Mitofusin 2 loss-of-function mutations are reported in CMT with autosomal dominant transmission or with spontaneous manifestations. Today, it is unknown how to activate the defective mitofusin protein, and there is currently no way of correcting MFN2 fusion and motility dysfunctions. Recently, we developed a small molecule, mitofusin functional activator, that breaks the mitofusin’s intramolecular bond, allowing for mitochondrial fusion in CMT2A mouse. The central goal of this proposal is to help design human therapeutic trial approaches for CMT2A patients.