Project description
Delivering therapeutics for Alzheimer’s disease to the brain
The blood-brain barrier (BBB) is a highly selective semipermeable barrier that separates circulating blood from the brain and prevents the entry of harmful substances while allowing essential nutrients to pass through. Although it protects the central nervous system, at the same time, it poses a barrier to the delivery of therapeutics to the brain to treat brain and neurological disorders. Funded by the Marie Skłodowska-Curie Actions programme, the Beyond the BBB project proposes to develop a nerve growth factor (NGF)-based therapeutic intervention for Alzheimer’s disease as NGF promotes neuronal survival. Researchers will evaluate two different approaches: they will either modulate the BBB through focused ultrasounds or deliver NGF through transferrin receptor-mediated transport.
Objective
Alzheimers disease (AD) is a neurodegenerative disease affecting the aged population and is projected to increase 3-fold in the next 30 years. Treatment options in AD are limited due to complex pathological processes and the blood-brain barrier (BBB), which restrict entry molecules into the brain. A finding in AD is the loss of cholinergic neurons. Tropomyosin receptor kinase A (TrkA) and its substrate, the nerve growth factor (NGF), are involved in neuronal survival and have been evaluated in small clinical trials as a therapeutic intervention in AD. Advances in BBB shuttling methods, in which antibodies and enzymes can be transported over the BBB, make NGF a possible treatment option in AD.
Within this proposal, I will develop novel methods for the delivery of NGF into the brain. Two different approaches for BBB delivery of NGF will improve the success rate. In one approach, NGF will be delivered into the brain by transferrin receptor (TfR)-mediated transcytosis. NGF will be chemically conjugated to a TfR binding antibody using a linker that selectively and quantifiably can release NGF in its native form in the brain, ensuring retained biological activity. An alternative approach, BBB will be opened with focused ultrasounds allowing passage of NGF into the brain. Positron emission tomography occupancy studies with [18F]TRACK, a TrkA selective tracer, will be used to evaluate in vivo binding of NGF to TrkA. The above-described BBB transport methods for NGF will be evaluated in long-term therapeutic study using 5xFAD mice. Pharmacodynamic readouts will be changes in brain amyloid-beta levels, neuroinflammation parameters and improved memory and cognitive functions. In this project, I will expand my knowledge in BBB delivery of macromolecules, learn new radiolabeling techniques from a world-leading radiochemist, and novel develop the necessary skills to take my career to the next level.
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.
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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.
This project's classification has been validated by the project's team.
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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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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
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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-MSCA-2022-PF-01
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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
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