# Complex inflammatory mechanisms and therapeutic targeting in endometriosis

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2021 · $415,069

## Abstract

PROJECT SUMMARY/ABSTRACT
Endometriosis is estimated to affect 10% of reproductive age women. It results in considerable morbidity with
chronic and debilitating pain, which substantially affect the quality of life of women and their families. Because
it is an estrogen-dependent disorder, hormonal therapies are available for the medical treatment of
endometriosis. However, these hormonal treatments along with laparoscopic surgery are often of limited
efficacy with high recurrence rates, frequent side effects, additional costs, and potential morbidity. Thus, a
critical need exists to develop new and effective therapies for endometriosis targeting biologically important
mechanisms that underlie pathophysiology of this disease. Endometriosis is known as a chronic inflammatory
disease. Aberrant inflammatory dysfunction contributes to development and progression of the disease. We
have recently determined a small molecule, niclosamide (Niclo) that could serve as a potential new effective,
non-hormonal, fertility-sparing option for the treatment of endometriosis. We have demonstrated that Niclo
reduces growth and progression of endometriosis-like lesions (ELL) via inflammatory signaling using a mouse
model of endometriosis. Our studies show that large peritoneal MΦ (LPM) are increased in the peritoneal fluid
(PF) of ELL mice and invaded into the ELL. Elevated LPM populations in the PF are reduced by Niclo. Niclo
also inhibits aberrant inflammation established in the PF, ELL, pelvic organs (uterus and vagina) and dorsal
root ganglion (DRG), as well as MΦ infiltration, vascularization and innervation in the ELL. Therefore, we
hypothesize that understanding the complex chronic inflammatory mechanisms associated with endometriosis
is crucial to develop a new therapeutic strategy and provides the rationale for targeting immune dysfunction.
The objective of this application is to test this hypothesis by examining: 1) how loss of LPM impacts
pathophysiology of endometriosis, 2) how ELL induction alters the functionally heterogenic population of ELL
and peritoneal exudate cells, and how their inflammatory dysfunction is inhibited by Niclo and 3) how inhibitory
interactions from Niclo correlate with pain-related symptomology. Niclo is an efficacious Food and Drug
Administration-approved drug for the treatment of helminthosis in humans that has been used for decades.
Thus, drug re-purposing of Niclo could result in a rapidly-distributable, fertility-sparing and effective non-
hormonal therapy that has fewer side effects than current treatments.

## Key facts

- **NIH application ID:** 10178341
- **Project number:** 1R01HD104619-01
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** KANAKO HAYASHI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $415,069
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10178341

## Citation

> US National Institutes of Health, RePORTER application 10178341, Complex inflammatory mechanisms and therapeutic targeting in endometriosis (1R01HD104619-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10178341. Licensed CC0.

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