Histone Deacetylase Inhibitors as Therapeutics for Endometriosis

Xin Li; Xishi Liu; Sun-Wei Guo


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

In This Article


Accumulating evidence strongly suggests that endometriosis is an epigenetic disease and, as such, is amenable for epigenetic therapy. By enumerating all desirable features of HDACIs, it is evident that HDACIs, as candidate therapeutics for endometriosis, have a lot of potential. Unfortunately, so far they have been greeted with concerns over safety, despite, in the case of VPA, the proven safe record. Since all drugs have, to a lesser or greater degree, side effects, it is important to understand what the acceptable risk–benefit ratio is. Given the fact that the current medications for treating endometriosis all have side effects of various kinds, VPA, given its many desirable traits, probably is no worse in safety profiles than any other drug.

Drug R&D is a notoriously long, arduous and costly process,[136,137] especially for de novo drugs. Endometriosis drug R&D is no exception. In light of this, it should be noted that drug repurposing is also a viable option for drug R&D. In fact, the climate is also favorable for research in drug repurposing. With favorable legislative changes in the Food, Drug and Cosmetic Act, such as the Hatch–Waxman Amendments, there is a growing interest in drug repurposing (or repositioning.)[138–141] Indeed, under the 505(b)(2) section of the Food, Drug and Cosmetic Act,[203] applications through drug repurposing can be offered temporary protection for new molecular entities; new dosage forms; new administration routes; new indications; and new new molecular entities combinations. The most rewarding of these research objectives from a scientific viewpoint is the discovery of novel therapies for unmet clinical needs,[142] such as medical treatment of endometriosis. Such a process seems more attainable via drug repurposing[141] as opposed to de novo drug discovery. Viewed from this perspective, one can argue that the choice of VPA is fully justifiable given all its desirable features.

Of course, there are still many unsolved issues regarding the mechanisms of action for HDACIs. For example, in treating endometriosis what kind of HDACIs, pan or specific, have the best risk–benefit ratio? To answer this question, one may need to determine the expression levels of HDACs in ectopic and eutopic endometria and other tissues.

With more research, it may be easier to come closer to a full understanding of the etiopathogenesis of endometriosis. Treatment or perhaps prevention of this unrelentingly painful and dreadful disease may also be possible.