Rimegepant, a CGRP peptide antagonist approved for migraines, reduced endometriosis cell growth in lab and patient-derived organoid models, suggesting potential for drug repurposing.
2 of 3 patient-derived models respondedRimegepant showed concentration-dependent antiproliferative effects in patient-derived endometriosis organoids
What the researchers found
ROR1 was found to be transcriptionally upregulated and overexpressed at the protein level across endometriosis lesions in a dataset of 408 endometriosis samples and 53 controls, validated in 179 tissue microarray samples.
Of three shortlisted compounds (rimegepant, cabergoline, pirenzepine), only rimegepant — a clinically approved CGRP antagonist — significantly reduced viability in 12Z endometriotic cells. In patient-derived organoids from deep infiltrating endometriosis, two of three models showed concentration-dependent antiproliferative and cytotoxic effects with morphological features consistent with cell death, while one model was less responsive.
Why it matters
Endometriosis affects roughly 10% of reproductive-age women and current treatments are mostly hormonal with significant side effects. Finding that an already-approved, well-tolerated migraine drug targeting CGRP peptide signaling could inhibit endometriosis growth opens a faster path to clinical testing than developing a new drug from scratch. This is among the first evidence connecting CGRP antagonism to endometriosis treatment.
How the study worked
Researchers first analyzed ROR1 expression in transcriptomic datasets (408 endometriosis samples, 53 controls) and validated protein-level expression in tissue microarrays (179 tissues). They used the BLAZE computational platform to identify drugs predicted to bind ROR1, filtered for safety, and screened three candidates in the 12Z endometriotic cell line. The most promising compound, rimegepant, was further tested in three patient-derived organoid models representing deep infiltrating endometriosis.
What this study cannot tell us
This is entirely preclinical with no human clinical data. Only three patient-derived organoid models were tested, and one did not respond, highlighting patient-specific variability. The study used an in vitro screening approach and has not demonstrated efficacy in animal models or humans. The mechanism by which rimegepant affects endometriosis cells (whether through ROR1, CGRP receptor, or another target) is not fully clarified. The concentrations used in lab models may not reflect achievable drug levels in human tissue.
How to read the evidence
This is an early-stage preclinical study combining computational drug screening with cell line and patient-derived organoid experiments. While the integrated approach is rigorous for this stage of research, no animal or human clinical data exists yet. The small number of organoid models (3) limits generalizability.
When this study was published
Published in 2025, this is a very recent study representing the first evidence of CGRP antagonist activity against endometriosis in human-derived models.
The bigger picture
CGRP has been primarily studied in the context of migraine and pain signaling, but this study suggests its role may extend to chronic inflammatory conditions like endometriosis. The success of repurposing a CGRP peptide antagonist highlights how understanding peptide signaling pathways can unexpectedly open new therapeutic avenues across different disease areas.
Questions still open
- Does rimegepant's effect on endometriosis cells work through CGRP receptor antagonism, ROR1 binding, or another mechanism?
- Could rimegepant reduce both pain and disease progression in endometriosis patients, given its dual relevance to pain signaling and cell growth?
- What explains the patient-specific variability in organoid responses, and could this guide personalized treatment approaches?
Common questions
What is CGRP and why might blocking it help with endometriosis?
Could someone with endometriosis start taking rimegepant now based on this study?
Read the original research
An integrated multimodal approach to drug repurposing in endometriosis, using ROR1 as a target.
Frontiers in pharmacology, 16, 1716062
Citation
Gunther, Kate; Liu, Dongli; Stannard, Gill; Holmes, Melissa; Loo, Christine; Guo, Belinda; Bowden, Nikola; Abbott, Jason; Ford, Caroline E. (2025). An integrated multimodal approach to drug repurposing in endometriosis, using ROR1 as a target.. Frontiers in pharmacology, 16, 1716062. https://doi.org/10.3389/fphar.2025.1716062