Project description
Peptide-drug conjugates preventing weight regain
The global obesity epidemic poses a challenge to human health. While effective weight-loss therapies exist, long-term maintenance remains difficult due to the body’s natural drive to regain lost weight. In response to food deprivation, specific hunger-promoting neurons become more excitable, triggering weight recidivism. The ERC-funded PDC-MAIN project aims to prevent this process by developing innovative peptide-drug conjugates (PDCs) that target the cellular mechanisms underlying homeostatic weight regain. By focusing on G protein-coupled receptors (GPCRs) in hypothalamic cells, the project will design GPCR-targeted PDCs to disrupt this cycle. Advanced neurobiological techniques, including fibre photometry, will be used to assess target engagement, while preclinical models will evaluate the potential for sustained weight loss following dietary and pharmacological interventions.
Objective
The worldwide rise in obesity rates is causing significant harm to human health. While effective weight loss therapies are emerging, the challenge of maintaining weight loss remains unresolved. With this project, we will leverage expertise in drug development to engineer novel peptide-drug conjugates designed to obstruct homeostatic weight regain in a cell specific fashion. In the food deprived state, a subset of hunger promoting neurons undergo structural changes that increases excitability and thus drives homeostatic weight regain. Capitalizing on our knowledge of G protein-coupled receptors (GPCRs) expressed in hypothalamic cell populations we will develop GPCR-targeting peptide-drug conjugates specifically designed to obstruct weight recidivism. To evaluate this drug-targeting approach, neurobiological methods including fiber photometry will be employed to confirm target engagement. Preclinical models are used to investigate the translational potential for treatment of weight loss maintenance following dietary and pharmacological weight loss interventions. The molecular mechanisms of action and receptor-target selectivity of the conjugates will be determined using loss-of-function mouse models. Pharmacokinetic properties of lead candidates will be optimized by incorporating chemical half-life extenders. This bridging between medicinal chemistry, neuroscience and pharmacology will give rise to new multimodal molecules targeting homeostatic weight regain mechanisms to address a vastly growing unmet medical need for weight loss maintenance pharmacotherapies.
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.
- natural sciences biological sciences neurobiology
- engineering and technology materials engineering fibers
- medical and health sciences basic medicine pharmacology and pharmacy
- medical and health sciences health sciences nutrition obesity
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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)
MAIN PROGRAMME
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Topic(s)
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.
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
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.
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 - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2024-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1165 KOBENHAVN
Denmark
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.