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NANOPARTICLES FOR THERAPY AND DIAGNOSIS OF ALZHEIMER DISEASE

Objectif

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.

Champ scientifique

Mots‑clés

Programme(s)

Thème(s)

Appel à propositions

FP7-NMP-2007-LARGE-1
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Régime de financement

CP-IP - Large-scale integrating project

Coordinateur

UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Contribution de l’UE
€ 2 930 387,00
Adresse
PIAZZA DELL'ATENEO NUOVO 1
20126 Milano
Italie

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Région
Nord-Ovest Lombardia Milano
Type d’activité
Higher or Secondary Education Establishments
Contact administratif
Fiorenza Coviello (Ms.)
Liens
Coût total
Aucune donnée

Participants (18)

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Dernière mise à jour: 25 Mai 2022

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Permalink: https://cordis.europa.eu/project/id/212043/fr

European Union, 2024