In Duchenne muscular dystrophy (DMD), deficiency of dystrophin leads to cardiomyocyte membrane instability, abnormal calcium influx, and progressive fibrotic remodeling of cardiac tissue. Histone deacetylase 6 (HDAC6) contributes to disease progression by regulating cytoskeletal dynamics and proteostasis in dystrophic muscle cells. Consequently, inhibition of HDAC6 represents a potential therapeutic strategy for addressing both the skeletal and cardiac manifestations of DMD.
Heart failure with preserved ejection fraction (HFpEF) has limited treatment options and remains a medical challenge. HFpEF is characterized by diastolic dysfunction with a normal ejection fraction. Previous findings have shown that inhibiting histone deacetylase 6 (HDAC6) alters the mechanisms contributing to dilated cardiomyopathy.
Tenaya Therapeutics Inc. has received FDA clearance of its IND application to begin clinical testing of TN-301, a highly selective small-molecule inhibitor of histone deacetylase 6 (HDAC6) initially being developed for heart failure with preserved ejection fraction (HFpEF).
Several genetic studies in a range of model organisms have pointed to an important role for the B-cell lymphoma 2 (BCL2)-associated athanogene 3 (BAG3) gene in the maintenance of cardiac function.
