Reducing the Progression of Endometriosis with Short Treatment of Corticotropin-Releasing Hormone Receptor Antagonist

Background

Associations between stress, hypothalamic pituitary adrenal axis (HPA) dysregulation, and the severity of endometriosis have been described. Corticotropin-releasing hormone (CRH) is a neuropeptide released in response to stress, and one of the main signaling factors within the HPA axis. CRH and corticotropin-releasing hormone receptors (CRHR1 and CRHR2) have been associated with endometriosis and are well-documented in stress-related disorders, reproductive function, and inflammation.

Technology Overview

Robust evidence from pre-clinical and clinical studies suggest that abnormal functioning of the HPA axis —release of CRH and the subsequent activation of inflammatory responses— disrupts the feedback of both neuroendocrine and immune systems, contributing to the progression of endometriosis. CRH acts mainly by binding to CRH receptors CRHR1 and CRHR2, with 10 times greater affinity for CRHR1. No studies have addressed antagonizing CRHR1 to treat endometriosis.

This technology entails antalarmin treatment for the reduction of endometriosis development and progression. Antalarmin is a non-peptide antagonist of CRHR1, widely used in pre-clinical studies to investigate the effects of CRH on reproduction, inflammation, addictive behavior, and sleep disorders. Both anti-stress and anti-inflammatory activities of antalarmin have been documented in animal studies. A single week of antalarmin administration after endometriosis induction in a rat model reduced the size of endometriotic vesicles by 67%, and the number of vesicles by 30%, upon 53 days of treatment completion (see Figure 1 for experimental details). Therefore, a short-term treatment produced long-lasting therapeutic effects. Antalarmin also prevented the increase in CRH and CRHR1 mRNA levels within endometriotic vesicles.

Further Details:

• Appleyard CB, Flores I, Torres-Reverón A (2020) The Link Between Stress and Endometriosis: from Animal Models to the Clinical Scenario. Reprod Sci Thousand Oaks Calif. https://doi.org/10.1007/s43032-020-00205-7 PMID: 32542543
• Torres-Reverón A, Rivera-Lopez LL, Flores I, Appleyard CB (2018) Antagonizing the corticotropin releasing hormone receptor 1 with antalarmin reduces the progression of endometriosis. PLoS ONE 13(11):e0197698. https://doi.org/10.1371/journal.pone.0197698 PMCID: PMC6235236

Stage of Development

The Technology Readiness Level (TRL) is estimated at 5.

Benefits

• Short-term administration to achieve long-term therapeutic effect
• Proven clinical safety
• Does not target gonadal hormones
• Readily crosses the blood-brain-barrier

Applications

• Treatment for endometriosis symptoms
  • Reduces size and quantity of endometriotic lesions
  • Alleviates pain, stress and anxiety

Opportunity

• Research support
• Commercial partnership