Monday, March 5, 2007
A pair of recently published papers highlight two possible therapeutic areas for histone deacetylase inhibitors outside of cancer: preventing heart failure and treating spinal muscular atrophy.
Several HDAC inhibitors are in Phase II trials for cancer, where it is believed that HDACs repress transcription of tumor suppressor genes, and it is known that several oncogenes inappropriately recruit HDACs.
The recent heart failure study pinpoints a specific HDAC - HDAC2 - that mediates the cardiac hypertrophic response indirectly through a GSK-3 beta-dependent pathway. The SMA study shows that HDAC inhibition can directly increase levels of survival motor neuron protein and rescue mice from disease.
Previous research has provided evidence that HDAC inhibitors can block cardiac hypertrophy, and at least two companies have announced that they are researching HDAC inhibitors for the indication. Now, researchers at the University of Pennsylvania School of Medicine have published in Nature Medicine the identification of a specific HDAC that regulates the cardiac hypertrophic response - HDAC2 - as well as part of its mechanism.