MCW Office of Technology Development

Sun-Wei Guo, PhD

Endometriosis is one of the most common gynecological diseases, affecting more that 5.5 million women in North America alone. The two most common symptoms of endometriosis are pain and infertility. The current medical treatment for endometriosis includes Gonadotropin Releasing Hormone (GnRH) agonists (e.g. goserelin and leuprolide), progesterone (e.g. methoxyprogesterone) and androgens (e.g. danazol).

All 3 types of drug treatments have unwanted side effects to varying degrees, such as weight gain, depression, acne, increased body hair and irregular bleeding. With all conventional endometriosis drug therapies, complete cure is uncommon, since the implants remain attached to organs and may resume monthly bleeding when therapy ends.

Dr Guo has discovered that certain genes are aberrantly methylated in eutopic or ectopic women with endometriosis and that DNA methyltranserases 1, 3A, and 3B are over-expressed in ectopic endometrium. To determine if endometriosis is an epigenetic disease, Dr Guo showed that histone deacetylase inhibitors (HDACIs) suppress proliferation of endometrial cells in vitro. In fact, they are more potent in proliferation inhibition than a promising class of compounds called selective progesterone receptor modulators (SPRMs), which have been shown in animal studies to be effective in suppressing proliferation of endometrial cells in vivo. In addition, HDACIs have a much better long-term suppression effect than SPRMs.
   
Suppression of proliferation is the key to the successful treatment of endometriosis. HDACIs, which have previously been proven effective in suppressing proliferation in many cancer cells, are affective in treating endometriosis through proliferation inhibition and, more importantly, correction of gene dysregulation (i.e. restoration of aberrant gene expression), which existing medications cannot achieve. Two HDACI drugs, valproic acid (VPA) and suberonilamide hydroxamic acid (SAHA) are currently approved for treating seizures and cancer, respectively.

• Suppresses proliferation of endometrial cells
• Restores aberrant gene expression
• Off label pilot study on endometriosis patients demonstrated effective relief of pain
• Utilizes well understood class of compounds that includes FDA approved drugs

This technology has been tested through in vitro studies. A pilot study using valproic acid (VPA) on endometriosis patients in China has been completed.