Marie Goret
Award winner 2026

Summary of the work

DNM2, encoding a GTPase involved in endocytosis and membrane dynamics, is mutated in two distinct disorders: centronuclear myopathy (CNM) and Charcot-Marie-Tooth neuropathy (CMT). While CNM is caused by gain-of-function mutations, the mechanisms underlying CMT remained unclear. This research highlights that CMT results from loss of DNM2 function and, strikingly, that CNM and CMT mutations can mutually compensate. Their combination restores biochemical activity in vitro and rescues neuromuscular phenotypes in vivo. These findings establish an unprecedented paradigm in which two pathogenic mutations in the same gene counterbalance each other and provide the first proof-of-concept that increasing DNM2 activity represents a therapeutic strategy for DNM2-CMT. More broadly, they open new avenues for targeting membrane trafficking pathways in inherited neuropathies.