Objective
Research objectives and content
Taking into account that the two relevant organs involved in the replication of the TSE agents (or priors) and accumulation of PrPsc (prion protein scrapie) are the spleen and the brain, we have conceived two approaches, based on the use of nanoparticles of chitosan as drug delivery systems, for contributing to the comprehension of the prion diseases:- the first aim consists in the evaluation of the effects induced by the selective targeting to the spleen of compounds which are supposed to inhibit the accumulation of the PrPsc:- Inhibition of PrP synthesis by an antisense oligonucleotide strategy. - Inhibition of Prpsc accumulation (transconformation?) by polyene antibiotics. - Destruction of target cells supporting PrPsc accumulation in spleen with clodronate.- the second one is to investigate in vivo the role of the microglial cells in the pathogenesis of TSEs. These cells have been proven to be indispensable for neuronal toxicity of PrPsC in vitro and a strategy of depletion will be used in vivo. The working system will be to engraft murine embryonic nervous system hyperexpressing PrP in the brain of mice lacking PrP. The graft tissue will be depleted in vitro for microglial cells with LLME (L-leucin methyl ester) or clodronate before grafting. The microglial depletion will then be maintained in vivo by the delivery of the same molecules with drug carrier systems.This research proposal could also open new perspectives for the pharmacological treatment of scrapie in experimental models.
Training content (objective, benefit and expected impact)
The use of targeted nanoparticulate formulations able to deliver anti-PrP oligonucleotides and other anti-PrP compounds to the brain and to the spleen may allow to highlight some crucial aspects of the pathogenetical mechanisms involved in prion diseases. This research could open new perspectives for the pharmacological treatment of prion diseases. Moreover, this research project will lead to progress in drug delivery systems, especially in the new nanoparticulate formulations for brain delivery. This would represent a major step ahead not only for the treatment of prion diseases but also of other neurodegenerative conditions including Alzheimer's disease. In addition, formulations for oligonucleotide delivery to humans may emerge from the proposed research.
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
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- engineering and technology nanotechnology nano-materials
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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.
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.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
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.
Coordinator
92296 Chatenay - Malabry
France
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.