Laurent Schaeffer’s team in Lyon, in collaboration with a Canadian team in Ottawa, has shown that inhibition of cytoplasmic histone deacetylase 6 (HDAC6) by administration of tubastatin A to mdx mice results in :
- an improvement in their strength,
- a decrease in muscle atrophy and fibrosis,
- an increase in utrophin and beta-dystroglycan levels,
- inhibition of the TGF-β signalling pathway by targeting Smad3,
- restoration of the microtubule network and the organisation of the neuromuscular junction.
Thus, the specific inhibition of HDAC6 could represent a new pharmacological therapeutic avenue in Duchenne muscular dystrophy (DMD).
It should be noted that givinostat, a histone deacetylase inhibitor, is already in clinical trials in Duchenne muscular dystrophy.
