What are histone deacetylase (HDAC) inhibitors ?
HDAC inhibitors work by adding an acetyl group to histones. Histones are proteins that are associated with DNA and regulate gene activity. TSA (trichostatin A) is an example of a HDAC inhibitor which is being studied both as a breast cancer therapy drug and has been studied in both the mdx mouse model (Duchenne) and sarcoglycan deficient mouse model (LGMD). How do histone deacetylase (HDAC) inhibitors work to treat muscular dystrophy? HDAC inhibitors work by increasing follistatin which antagonizes myostatin. This is yet another example of how inhibiting myostatin improves muscular dystrophy (see prior posts on myostatin inhibition through propetide, ACE-031). It is still unclear if myostatin inhibition will have a therapeutic effect in the CMDs. What is HDAC2? HDAC2 is a histone deacetylase enzyme. Dr. Puri showed that a mutation in dystrophin leads to an increas in the amount of HDAC2. When he inhibited HDAC2 with an HDAC inhibitor, the dystrophic muscle cells returned to a normal hi
