Therapeutics For Endometriosis Research Articles

Diagnostic and therapeutic approaches for endometriosis: a patent landscape.

The aim of this review is to analyze the patent filings and to systematize the main technological trends in patent protection for the diagnosis and therapeutics for endometriosis. Patent literature has also been explored to identify active inventors and applicants in this field. Patent search was carried out in the freely accessible patent search databases namely, patentscope using various combinations of the keywords "Endometriosis OR Adenomyosis" AND "Diagnostic OR Therapeutics" were used along with wildcard search queries in the "Title", "Abstract" and "Descriptions" fields. A patent search revealed 144 patents describing inventions for diagnostic and therapeutic purposes of endometriosis. These patents include 26 patent applications in the diagnostic utility and 116 patent applications under the therapeutic approaches. Out of these 116 patent applications, 43 describe traditional medicines for endometriosis. Two patent applications describe inventions that can fall into both categories. Efforts are being made to improve current diagnostic instruments.Hormonal alteration methods is the most common field of invention, followed by surgical interventions for therapeutics. A general trend of increase in patent application filings has been observed with a slight decrease in recent years.

Mitochondrial translocation of estrogen receptor β affords resistance to oxidative insult-induced apoptosis and contributes to the pathogenesis of endometriosis

Endometriosis is the major cause of female infertility and has been linked to the action of estrogen and estrogen receptor (ER). A new pool of ERβ locates within mitochondria, which regulates the endometriotic cell withstanding external insults, but its effect remains controversial. We hypothesize that mitochondrial estrogen receptor ERβ (mtERβ) is a pivotal regulator in estradiol-mediated cell protection leading to the endometriotic progression. We observed elevated levels of ERβ in the endometriotic tissues. A dramatic increase of ERβ in mitochondria (mtERβ) was found in the ectopic endometriotic tissues, or the estradiol-primed primary endometriotic cells. We analyzed the mtERβ-specific overexpressing clone (mtsERβ), which exhibited higher mitochondrial bioenergetics and lower reactive oxygen species (ROS) generation. The mtsERβ-overexpressed endometriotic cells displayed an enhanced migration phenotype, whereas significantly attenuated migration by mitochondrial respiratory inhibitor (oligomycin) or ERβ deficiency by shERβ. Further investigations revealed that ERβ directly modulated mitochondrial DNA (mtDNA) gene expression by interacting with mtDNA D-loop and polymerase γ. The mtsERβ afforded a resistance to oxidative insult-induced apoptosis through the induction of the ROS scavenger enzyme Mn-superoxide dismutase and anti-apoptotic protein Bcl-2. Collectively, the demonstration of mtERβ responses in restoration of mitochondrial bioenergetics and inhibition of mitochondria-dependent apoptotic events provides insight into the pathogenesis of endometriosis, suggesting ERβ-selective estrogen receptor modulator may serve as novel therapeutics of endometriosis in the future.

Histone deacetylase inhibitors as therapeutics for endometriosis

Endometriosis is a common gynecological disorder affecting mostly women of reproductive age. Its presenting symptoms include dysmenorrhea, chronic pelvic pain and infertility. There is a pressing need to develop more efficacious therapeutics, preferably with improved safety and cost profiles. Unfortunately, thus far the drug development progress has been frustratingly slow. In this article, published data in support of the notion that endometriosis is an epigenetic disease are reviewed. The desirable properties of histone deacetylase inhibitors as therapeutics for treating endometriosis are enumerated, and the obstacles in evaluating histone deacetylases in clinical trials are listed. It is argued that, from the drug discovery standpoint, repurposing of valproic acid is justifiable. Finally, the areas in need of further research are exposed.

Cutting SRC-1 down to size in endometriosis

Endometriosis is an estrogen-dependent disease. The biologically active estrogen, estradiol, aggravates the pathological processes (e.g., inflammation and growth) and the symptoms (e.g., pain) associated with endometriosis. Abundant quantities of estradiol are available for endometriotic tissue via several mechanisms including local aromatase expression. The question remains, then, what mediates estradiol action. Because estrogen receptor (ER)β levels in endometriosis are >100 times higher than those in endometrial tissue, this review focuses on this nuclear receptor. Deficient methylation of the ERβ promoter results in pathological overexpression of ERβ in endometriotic stromal cells. High levels of ERβ suppress ERα expression. A severely high ERβ-to-ERα ratio in endometriotic stromal cells is associated with suppressed progesterone receptor and increased cyclo-oxygenase-2 levels contributing to progesterone resistance and inflammation. ERβ-selective estradiol antagonists may serve as novel therapeutics of endometriosis in the future.

Role of Estrogen Receptor-β in Endometriosis

Endometriosis is an estrogen-dependent disease. The biologically active estrogen, estradiol, aggravates the pathological processes (e.g., inflammation and growth) and the symptoms (e.g., pain) associated with endometriosis. Abundant quantities of estradiol are available for endometriotic tissue via several mechanisms including local aromatase expression. The question remains, then, what mediates estradiol action. Because estrogen receptor (ER)β levels in endometriosis are >100 times higher than those in endometrial tissue, this review focuses on this nuclear receptor. Deficient methylation of the ERβ promoter results in pathological overexpression of ERβ in endometriotic stromal cells. High levels of ERβ suppress ERα expression. A severely high ERβ-to-ERα ratio in endometriotic stromal cells is associated with suppressed progesterone receptor and increased cyclo-oxygenase-2 levels contributing to progesterone resistance and inflammation. ERβ-selective estradiol antagonists may serve as novel therapeutics of endometriosis in the future.

Effects of PRL-3 siRNA on the migration of endometriotic stromal cells

To evaluate the effects of PRL-3 siRNA (small interfering RNA) on the migration of endometriotic stromal cells. Primary endometriotic stromal cells were cultured in vitro. Then PRL-3 (phosphatase of regenerating liver-3) siRNA was transfected to silence the PRL-3 gene. And the PRL-3 protein expression was analyzed by Western blot. The changes of cell migration were detected by cell pseudopod formation, scratch test and transwell cell migration test. The expression of PRL-3 protein significantly decreased in the experimental group versus two other control groups (P < 0.05). The formation of cell pseudopod was much less in experimental group than that in control groups. Within the same time, the number of migration cells was 0.87 ± 0.21 in experimental group. It was less than 1.75 ± 0.28 in blank control group and 1.63 ± 0.39 in negative control group (P < 0.05). PRL-3 siRNA can down-regulate the PRL-3 gene and decrease the migratory capacity of endometriotic stromal cells. And PRL-3 may be a promising target in the therapeutics of endometriosis.

Clinical trials and trial-like studies on the use of traditional Chinese medicine to treat endometriosis

There is a pressing need for the development of new therapeutics for endometriosis, and traditional Chinese medicine (TCM) is likely to be a treasure trove that will help to achieve this aim. We retrieved 851 papers on clinical studies evaluating the use of TCM to treat endometriosis that were published in the last 16 years and evaluated 153 of them that met our inclusion criteria. We found that the quality of these studies is well below an acceptable level, making it difficult to judge whether TCM is truly efficacious. There are signs that these studies, as a whole, have serious anomalies. The most glaringly deficient areas are informed consent, bias in evaluating outcome measures, follow-up, diagnosis, data analysis, report of adverse events and randomization. The uniformly low quality is alarming, given the large quantity of these studies, the enormous resources and energy put into these studies and, above all, the weighty issue of treatment efficacy that concerns each and every patient with endometrio...

Emerging drugs for endometriosis

Background: Endometriosis is a benign, common gynecological disorder affecting mostly women of reproductive age. It is associated with dysmenorrhea, pelvic pain, and subfertility. The current non-surgical medical treatment is not satisfactory and there is a pressing need for novel therapeutics with better efficacy, tolerability and safety profiles. Objective: To investigate the development of new therapies for endometriosis. Methods: The PubMed database has been extensively searched for all compounds tested preclinically and clinically. Results/conclusion: Besides the three main classes of drugs, i.e., GnRH agonists, progestins, and androgenic agents, there are several classes of compounds that have been tested preclinically and clinically. Surprisingly, a considerable proportion of officially registered Phase II/III clinical trials are listed as completed yet no information on their outcomes is available. Three completed and published Phase II trials found the tested compound disappointing. Another two Phase II clinical trials have been suspended. This apparent gap between the generally promising preclinical findings and the clinical trial outcomes reflects our current woefully inadequate understanding of the mechanisms underlying endometriosis-associated pain and subferitility and recurrence of endometriosis; questions the adequacy and value of animal models of endometriosis that are still in use; highlights the difficulty in developing new therapeutics for endometriosis; and calls for more research in the mechanisms underlying endometriosis-associated pain and subferitility and recurrence of endometriosis.