TRPV4 neuromuscular disease registry highlights bulbar, skeletal and proximal limb manifestations.

ABSTRACT: Dominant missense mutations of the calcium-permeable cation channel TRPV4 cause Charcot-Marie-Tooth disease (CMT) type 2C and two forms of distal spinal muscular atrophy. These conditions are collectively referred to as TRPV4-related neuromuscular disease and share features of motor greater than sensory dysfunction and frequent vocal fold weakness. Pathogenic variants lead to gain of ion channel function that can be rescued by TRPV4 antagonists in cellular and animal models. As small molecule TRPV4 antagonists have proven safe in trials for other disease indications, channel inhibition is a promising therapeutic strategy for TRPV4 patients. However, the current knowledge of the clinical features and natural history of TRPV4-related neuromuscular disease is insufficient to enable rational c

SUBMITTER: Kosmanopoulos GP 

PROVIDER: S-EPMC12054732 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature