A presenter from UConn Health and The Jackson Laboratory described preclinical progress toward therapies for dilated cardiomyopathy caused by pathogenic variants in troponin T2 (TNNT2), including AAV-mediated gene replacement, engineered higher-activity proteins, and base-editing approaches.

The nut graf: Presenters said each approach has a distinct target population and risk–benefit profile: AAV replacement aims to outcompete mutant protein, engineered proteins aim to increase sarcomere force, and base editors seek to correct specific nucleotide variants—work that could lead to targeted therapies for subsets of patients with genetically defined cardiomyopathy.

Dr. Travis Henson summarized laboratory results in mouse models showing restoration of cardiac function and extended survival after AAV-delivered human TNNT2, improved outcomes with "tuned-up" TNNT2 constructs, and partial normalization of heart weight and function using adenine base editing targeted to a specific pathogenic nucleotide. "When we look at the histology...this is a nice striated and this is actually exactly what troponin should look like," Henson said, describing immunostaining of treated mouse hearts.

The team emphasized that these data are preclinical, that some approaches will only serve small, variant-defined subgroups, and that further studies in larger animals and safety testing will be needed before human trials.

Ending: Researchers said they will continue preclinical development and toxicology studies and that their objective is to advance one or more approaches toward clinical testing for genetically selected patient groups.