HDAC and DNMT Inhibitors such as Trichostatin A (TSA) and 5-aza-cytidine are preventative therapies and reduce myocardial infarct volume following cardiac events
Every 40 seconds, someone in the United States has a heart attack. Although several therapeutic options for heart attack recovery exist, ischemic injuries are responsible for a significant amount of morbidity and mortality throughout the world. New therapeutics that offer significant improvements for those already exposed to, or at risk for, ischemic injury are needed.
Drs. Epstein, Gruber, and Abdullah have shown several histone deacetylase (HDAC) and DNA methyltransferase (DNMT) inhibitors, epigenetic regulators, reduce the risk of and help heal ischemic injuries in animal models. The HDAC and DNMT inhibitors, small molecules such as Trichostatin A, reverse the effects of myocardial infarction by reducing infarction volume. The use of the epigenetic regulators alone, or in combination with known ischemic injury treatments, has therapeutic potential, and offers increased therapeutic efficacy for the healing or prevention of ischemic injuries such as heart attacks.
Inhibition of HDACs promotes cell survival during hypoxia in isolated cardiac myocytes. Quantitative evaluation. *P = 0.04; **P = 0.01; 500 cells counted in 5 fields for each condition; n = 3. (FASEB J. 2008 Oct;22(10):3549-60)
Small molecule therapeutics that prevent ischemic injury and reverse myocardial infarction effects
- HDAC inhibitors can be formulated into bioavailable oral agents
- Proven clinical efficacy for HDAC inhibitors in other human diseases
- Seven candidates to advance into clinical development
Stage of Development:
Proof of concept in vivo
Granger, A. et al; FASEB 2008 Oct; 22(10) 3549.
Docket # R3701