Histone Deacetylase Inhibitors as Therapeutics for Endometriosis

Xin Li; Xishi Liu; Sun-Wei Guo


Expert Rev of Obstet Gynecol. 2012;7(5):451-466. 

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Expert Commentary

Developing more efficacious therapeutics for endometriosis, preferably with improved safety and cost profiles, is an unmet medical need. To fulfill this with the discovery of novel therapies is arguably the most rewarding research goal. Unfortunately, despite well over 100 published preclinical rodent efficacy studies of endometriosis that are often encouraging or even exciting and many more basic research studies, there seems to be a loss in translating discoveries made in basic and preclinical research into better therapies. This has caused some palpable disappointment among clinicians, and surely demands solutions.

Accumulating evidence suggests that endometriosis is an epigenetic disease and, as such, may be treatable by epigenetic therapy, such as HDACIs. Indeed, many in vitro, in vivo and clinical studies have shown that HDACIs have many desirable properties. Yet, to the authors' best knowledge, no clinical trial has ever been conducted or is planned to evaluate the efficacy and risk–benefit ratio. This lack of interest could stem from concerns of drug safety and also from the lack of financial incentives. Regardless, some HDACIs appear to be safe, and one of them, VPA, has an excellent safety record, except for, of course, its known teratogenic effect. All drugs, more or less, have side effects. Whether a drug is acceptable or not depends, ultimately, on the risk–benefit ratio. Yet without any clinical trials, the efficacy and safety of VPA or any other HDACIs will never be known. Drug R&D is a long, arduous and costly process with high attrition rate. With this in mind, giving VPA or other HDACIs a chance may be consistent with the spirit of drug repurposing in drug R&D.