Inhibiting desmosomal protein degradation in cardiomyopathy; plus senescence data from AKL and more

A Hubrecht Institute-led team, including Phlox Therapeutics B.V. co-founder and CSO Eva Van Rooij, reported in Science Translational Medicine that targeting the ubiquitin–proteasome system can prevent desmosomal protein degradation and instability that drives arrhythmogenic cardiomyopathy (ACM).

Analyses of heart tissues from ACM patients, cardiomyocytes derived from patient induced pluripotent stem cell (iPSC), and mice with a disease-driving PKP2 mutation linked decreased levels of desmosomal and adherens junction proteins with cardiac dysfunction and fibrosis. Inhibiting the ubiquitin proteasome system increased expression of area composita proteins, and improved calcium dynamics in cardiomyocytes isolated from a mouse model of ACM...