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Therapeutic targeting of FKBP51 for the prevention of stress-induced preterm birth

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HD113465-01
Agency Tracking Number: R41HD113465
Amount: $384,972.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NICHD
Solicitation Number: PA22-178
Timeline
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-08-01
Award End Date (Contract End Date): 2024-07-31
Small Business Information
3655 Nobel Drive, Suite 260
San Diego, CA 92122
United States
DUNS: 788494669
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 DAVID FRIEND
 (858) 926-7655
 dfriend@darebioscience.com
Business Contact
 SABRINA JOHNSON
Phone: (858) 926-7655
Email: sjohnson@darebioscience.com
Research Institution
 UNIVERSITY OF SOUTH FLORIDA
 
3702 SPECTRUM BLVD., SUITE 165
TAMPA, FL 33612
United States

 Nonprofit College or University
Abstract

In the United States, one in ten babies is born prematurely. The earlier in pregnancy a baby is born, the more
likely they will have an extended hospital stay, as well as serious health complications such as respiratory
distress syndrome, necrotizing enterocolitis, deafness, vision problems and cerebral palsy. Maternal stress is a
well-established risk factor for preterm birth, and recent studies using a mouse model of maternal stress highlight
the role of a stress response protein, FKBP51, in promoting preterm birth. Prior work demonstrates that stress
boosts FKBP51 expression. Consequently, FKBP51 binds to progesterone receptors in decidual cells at the
maternal-fetal interface, reducing progesterone receptor activity in the nucleus, resulting in the functional
withdrawal of progesterone that triggers labor and birth in humans. Importantly, this novel molecular pathway
can be blocked by 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2), restoring the activity of progesterone receptors
in vitro and in vivo. Thus, therapeutic targeting of FKBP51 has great potential as a safe and effective strategy to
prevent preterm birth. Because there exist no pharmacological strategies for the prevention of preterm birth,
Daré Bioscience, in collaboration with the University of South Florida, aims to rigorously demonstrate the
feasibility of targeting FKBP51 to improve obstetric treatment options for women. Work in Aim 1 is focused on
validating FKBP51 as a novel drug target using clinically-relevant human decidual cell culture models, selecting
a therapeutic strategy that combines 15dPGJ2 with delivery of a progestin, and evaluating the downstream
biological effects of treatment. The focus of Aim 2 is to demonstrate the in vivo safety and efficacy of 15dPGJ2
plus progestin combination therapy for pregnancy maintenance in a previously validated maternal stress induced
mouse model of preterm birth. The goal is to demonstrate a statistically significant increase in gestational length
by treatment(s) in stressed animals vs. untreated stressed controls. This project has significant translational and
commercial potential because it will provide the necessary proof-of-concept data to advance a treatment strategy
to Phase II IND-enabling studies.

* Information listed above is at the time of submission. *

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