Project description
A new approach to boosting brain function in Alzheimer’s
Millions of people worldwide suffer from cognitive decline caused by Alzheimer’s disease (AD) and other dementias, a problem that is increasing as populations age. Most drugs tested in clinical trials fail, and the few approved treatments do not improve memory or thinking abilities. They also come with serious side effects. Finding new ways to boost brain function remains crucial. The ERC-funded UPGRADE project investigates a promising new approach using gonadotropin-releasing hormone (GnRH), a neuropeptide linked to both reproduction and brain function. Research suggests that restoring GnRH in a natural, pulsatile pattern could improve cognition in AD patients. UPGRADE will test whether this therapy can safely enhance memory and thinking abilities.
Objective
Cognitive decline associated with Alzheimer disease (AD) and other age-related dementias affects ~55 million people worldwide, and is a growing problem in aging European societies. However, most drugs fail at clinical trial, and approved treatments aimed at controlling or reversing pathological changes in the brain do not improve cognition in patients, besides having significant side effects. It is thus essential to design and test alternative approaches to enhance cognitive performance and reduce the personal, familial and societal burden of AD.
There is abundant circumstantial evidence pointing to a correlation between cognitive decline or AD progression with the age-dependent loss or deregulation of gonadotropin-releasing hormone (GnRH), a neuropeptide better known for its role in the reproductive axis. Nevertheless, a link between the two processes has not been seriously considered. In a recent groundbreaking study, we have shown that AD-like cognitive deficits in Down syndrome stem from progressive GnRH loss, and restoring native GnRH in a physiologically relevant pulsatile pattern using implantable pumps safely and effectively improves cognition long after the onset of symptoms, together with augmented brain connectivity. Additionally, we have shown that tanycytes, specialized hypothalamic glial cells that control GnRH secretion, are fragmented in AD patient brains. Putting these two findings together, we hypothesize that cognitive performance in AD patients can also be enhanced by administering pulsatile GnRH at normally occurring doses, improving their quality of life,.
The UPGRADE project will extend promising results we have obtained on the effectiveness of this strategy in a preclinical mouse model of AD, analyze GnRH activity and pulsatility in an existing cohort of AD patients, and finally, draft a clinical trial protocol to test the safety and efficacy of pulsatile GnRH therapy to reactivate cognitive reserves in patients with mild/moderate AD.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants
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Call for proposal
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(opens in new window) ERC-2023-POC
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75654 Paris
France
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