Identifying therapeutic candidates for endometriosis through a transcriptomics-based drug repositioning approach

Existing medical treatments for endometriosis-related pain are often ineffective, underscoring the need for new therapeutic strategies. In this study, we applied a computational drug repurposing pipeline to stratified and unstratified disease signatures based on endometrial gene expression data to i...

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Published in:iScience 2024-04, Vol.27 (4), p.109388, Article 109388
Main Authors: Oskotsky, Tomiko T., Bhoja, Arohee, Bunis, Daniel, Le, Brian L., Tang, Alice S., Kosti, Idit, Li, Christine, Houshdaran, Sahar, Sen, Sushmita, Vallvé-Juanico, Júlia, Wang, Wanxin, Arthurs, Erin, Govil, Arpita, Mahoney, Lauren, Lang, Lindsey, Gaudilliere, Brice, Stevenson, David K., Irwin, Juan C., Giudice, Linda C., McAllister, Stacy L., Sirota, Marina
Format: Article
Language:English
Subjects:
Drugs
Transcriptomics
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Summary:Existing medical treatments for endometriosis-related pain are often ineffective, underscoring the need for new therapeutic strategies. In this study, we applied a computational drug repurposing pipeline to stratified and unstratified disease signatures based on endometrial gene expression data to identify potential therapeutics from existing drugs, based on expression reversal. Of 3,131 unique genes differentially expressed by at least one of six endometriosis signatures, only 308 (9.8%) were in common; however, 221 out of 299 drugs identified, (73.9%) were shared. We selected fenoprofen, an uncommonly prescribed NSAID that was the top therapeutic candidate for further investigation. When testing fenoprofen in an established rat model of endometriosis, fenoprofen successfully alleviated endometriosis-associated vaginal hyperalgesia, a surrogate marker for endometriosis-related pain. These findings validate fenoprofen as a therapeutic that could be utilized more frequently for endometriosis and suggest the utility of the aforementioned computational drug repurposing approach for endometriosis. [Display omitted] •We used a computational drug repurposing method to identify endometriosis treatments•Rarely prescribed NSAID fenoprofen emerged as a potential endometriosis therapeutic•Fenoprofen alleviated vaginal hyperalgesia in a rat model of endometriosis Drugs; Transcriptomics
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.109388