# Imaging and treatment of endometriosis in nonhuman primates

> **NIH NIH P01** · DUKE UNIVERSITY · 2024 · $373,905

## Abstract

Project 3: Imaging and treatment of endometriosis in nonhuman primates
SUMMARY/ABSTRACT
The overarching goal of this P01 Center is to advance our understanding of the pathophysiology of endometriosis
in order to improve the diagnosis and treatment of the disease in women. Endometriosis is a painful disorder of
women and nonhuman primates (NHPs) in which endometrium-like tissues form estrogen-dependent lesions
outside the uterus. There is currently no cure; all approved therapies target estrogen (E2) action to manage
symptoms, which is of limited use in reproductive-age women due to unwanted side effects. Macaques provide
excellent preclinical models for testing novel therapies that have not been fully vetted for clinical trials. However,
no reliable methods exist to detect early-stage disease in either women or monkeys, and improved diagnostic
approaches are needed to evaluate new therapies. Our premise is that endometriotic cell metabolism is a novel
target for improved therapies for the disease. This premise emanates, in part, from studies that have revealed
that consumption of an obesogenic "western-style" diet (WSD) combined with testosterone (T) treatment
increases the rate and severity of endometriosis in macaques. Furthermore, a key feature of endometriotic
lesions is the presentation of chronic peritoneal inflammation. Endometrial Sirtuin 1 (SIRT1) has been reported
as a biomarker of endometriosis. SIRT 1 mediates endometrial progesterone resistance associated with
endometriosis-induced infertility. Moreover, SIRT1 is a protein deacetylase enzyme that functions as a metabolic
sensor, regulating mitochondrial respiration and aerobic glycolysis. Increased understanding of the role of SIRT1
and other inflammatory and metabolic markers may help to identify more reliable methods of diagnosis and
treatment of endometriosis. Accordingly, in Specific Aim 1, we will refine positron emission tomography-
computed tomography (PET-CT) with estrogen and progesterone receptor-specific tracers. We will monitor
endometriotic lesion size and abundance in macaques by PET-CT and ultrasound and compare the results with
a laparoscopic examination, which is currently the "gold standard" for staging the disease. In Specific Aim 2,
we will evaluate cellular mediators of inflammation, progesterone resistance, and metabolic response in serum,
peritoneal fluid, endometrium, and endometrial lesions; and quantify immune cell infiltration in endometriotic
lesions from macaques. We will correlate these measures with the lesion burden detected by PET-CT and
laparoscopy. In Specific Aim 3, we will use the macaque endometriosis model to test the effect of inhibitors
against SIRT1 (Selisistat; EX-527) and the glycolytic enzyme, pyruvate dehydrogenase (dichloroacetate; DCA).
During each aim, macaque samples will be archived for future study, and relevant findings will be used to inform
Project 1 (Dr. Young, PI; involving PET/MRI imaging and inflammation of the disease in wom...

## Key facts

- **NIH application ID:** 10925404
- **Project number:** 5P01HD106485-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** OV D SLAYDEN
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $373,905
- **Award type:** 5
- **Project period:** 2021-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10925404

## Citation

> US National Institutes of Health, RePORTER application 10925404, Imaging and treatment of endometriosis in nonhuman primates (5P01HD106485-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10925404. Licensed CC0.

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