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NANOPARTICLES FOR THERAPY AND DIAGNOSIS OF ALZHEIMER DISEASE

Objetivo

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.

Ámbito científico

Palabras clave

Programa(s)

Tema(s)

Convocatoria de propuestas

FP7-NMP-2007-LARGE-1
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Régimen de financiación

CP-IP - Large-scale integrating project

Coordinador

UNIVERSITA' DEGLI STUDI DI MILANO-BICOCCA
Aportación de la UE
€ 2 930 387,00
Dirección
PIAZZA DELL'ATENEO NUOVO 1
20126 MILANO
Italia

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Región
Nord-Ovest Lombardia Milano
Tipo de actividad
Higher or Secondary Education Establishments
Contacto administrativo
Fiorenza Coviello (Ms.)
Enlaces
Coste total
Sin datos

Participantes (18)

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Última actualización: 25 Mayo 2022

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

European Union, 2024