Objective
The search for effective therapies and early detection strategies for Alzheimer’s Disease (AD), the major cause of dementia in Europe, is imperative. It is known that β-amyloid (Aβ) peptide plays a central role in neurodegeneration. In AD brain, Aβ is released in a soluble form that progressively becomes insoluble forming aggregates; extracellular plaques mainly composed of Aβ are a hallmark of post-mortem brains. These premises strongly suggest brain Aβ as a possible target for therapy and diagnosis of AD. In addition, it is known that brain and blood Aβ pools are in equilibrium via the blood-brain-barrier (BBB). Accordingly, it has been reported that removal of blood Aβ may withdraw the excess of brain Aβ by a “sink” effect. Thus, blood Aβ is another potential target. The aim of this project is to utilize nanoparticles (NPs) specifically engineered for targeting brain Aβ, for the combined diagnosis and therapy (theranostics) of AD. NPs (liposomes, solid lipid NPs, polymeric-NPs) will be multiple-functionalized with: i) a large arsenal of molecules (specific lipids, antiamyloidogenic drugs, polyphenols, heteroaromatic compounds, unnatural peptides and peptidomimetics, antibodies) interacting with Aβ in all aggregation forms, ii) PET or MRI contrast agents detecting such interaction, iii) molecules stimulating BBB crossing via the transcytotic route. Several artificial and cellular models will be used to fine-tune such features and to improve NPs biocompatibility, non-immunogenicity, non-toxicity and physical stability. Eventually, absorption, distribution, metabolism and excretion will be studied using animal models of AD. Different routes (i.v. oral, nasal) and protocols (two-step, NPs cocktails, aerosols) of administration will be utilized to boost NPs brain delivery. The prediction is that NPs will detect, disaggregate and remove Aβ brain deposits. In any case, NPs will interact with blood Aβ, withdrawing the excess of brain peptide by a “sink” effect.
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Keywords
Programme(s)
Call for proposal
FP7-NMP-2007-LARGE-1
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Funding Scheme
CP-IP - Large-scale integrating projectCoordinator
20126 MILANO
Italy
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Participants (18)
91405 ORSAY CEDEX
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845 Bratislava
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17177 Stockholm
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1105AZ Amsterdam
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2100 Goedoello
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20014 Turku
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10144 Torino
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265 04 Rio Patras
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2000 Antwerpen
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48940 Leioa
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LA1 4YW Lancaster
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20156 Milano
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2825 182 Caparica
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75252 PARIS
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93420 VILLEPINTE
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48008 BILBAO
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1165 Kobenhavn
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41013 Sevilla
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