SubsidieMeestersAntagonizing GnRH signaling as a “holistic” therapeutic strategy for Polycystic Ovary Syndrome
GRASP aims to test low doses of a GnRH antagonist to reduce LH hyper-pulsatility and improve reproductive and metabolic traits in PCOS, paving the way for future clinical trials.
Projectdetails
Introduction
PCOS is the most common endocrine disorder affecting up to 18% of women worldwide. The syndrome imposes a heavy health burden, covering infertility, obesity, type 2 diabetes, and metabolic syndrome.
Need for Treatment Options
The development of treatment options is an urgent need since there is currently neither a cure nor mechanism-based treatments. This leaves patient management suboptimal and focused solely on symptomatic treatment.
Neuroendocrine Aberration
One key neuroendocrine aberration in most women with PCOS is increased luteinizing hormone (LH) pulse frequency. This suggests an increase in the activity of gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus.
Role of LH Hyper-Pulsatility
The LH hyper-pulsatility contributes to increased ovarian thecal androgen secretion and failure of ovulation, constituting a pivotal pathogenic role in the syndrome. These evidences suggest that alterations of GnRH neuronal activity/secretion could be the basis for neuroendocrine anomalies that accompany the reproductive disturbances in the syndrome.
GRASP Hypothesis
In GRASP, we will test the hypothesis that low administration doses of a GnRH antagonist, aimed at tempering LH secretion/pulsatility, can ameliorate both reproductive and metabolic PCOS traits in animal models of PCOS and in women with PCOS.
Specific Objectives of GRASP
The specific objectives of GRASP are to:
- Dose-range GnRH antagonism to rectify LH pulse amplitude and frequency in PCOS-like mice.
- Perform a long-term treatment with the selected doses of GnRH antagonist to assess its potential beneficial outcomes in correcting reproductive and metabolic alterations of this preclinical model.
- Conduct a pilot dose-effect clinical investigation testing the ability of sub-therapeutic doses of GnRH antagonist to rectify the altered hormonal dynamics in women with PCOS.
Overall Goal
The overall goal of GRASP is to provide a proof-of-concept for future long-duration randomized controlled trials of this approach to appraise its clinical benefits in women with PCOS and to move forward towards therapeutic innovation.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 150.000 |
| Totale projectbegroting | € 150.000 |
Tijdlijn
| Startdatum | 1-9-2023 |
| Einddatum | 28-2-2025 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALEpenvoerder
- CENTRE HOSPITALIER REGIONAL ET UNIVERSITAIRE DE LILLE
Land(en)
Vergelijkbare projecten binnen European Research Council
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|---|---|---|---|---|
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The UPGRADE project aims to enhance cognitive performance in Alzheimer's patients by testing the safety and efficacy of pulsatile GnRH therapy based on promising preclinical results.
CenTral and PeRipheral NervoUs SyStem acTion of GIPR in ObEsity and Diabetes
This project aims to elucidate the mechanisms of GIPR (ant)agonists and GLP-1R/GIPR co-agonists in regulating energy and glucose metabolism to inform future obesity drug development.
Hormone-Induced Resistance to GLP-1 Receptor Agonists in Diabetes: Unraveling the Molecular Complexities
This project aims to understand how endogenous amidated hormones influence GLP-1RA effectiveness in T2DM to develop personalized therapies and improve patient outcomes.
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This project aims to explore the role of delta opioid receptors in insulin secretion to develop innovative drug targets for Type 2 diabetes, utilizing advanced genomic and pharmacological methods.
Building consensus for a new approach to breast cancer prevention in women with a BRCA1 mutation
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