Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
Invito a presentare proposte
FP7-NMP-2007-LARGE-1
Vedi altri progetti per questo bando
Meccanismo di finanziamento
CP-IP - Large-scale integrating projectCoordinatore
20126 MILANO
Italia
Mostra sulla mappa
Partecipanti (18)
91405 ORSAY CEDEX
Mostra sulla mappa
845 Bratislava
Mostra sulla mappa
17177 Stockholm
Mostra sulla mappa
1105AZ Amsterdam
Mostra sulla mappa
2100 Goedoello
Mostra sulla mappa
20014 Turku
Mostra sulla mappa
10144 Torino
Mostra sulla mappa
265 04 Rio Patras
Mostra sulla mappa
2000 Antwerpen
Mostra sulla mappa
48940 Leioa
Mostra sulla mappa
LA1 4YW Lancaster
Mostra sulla mappa
20156 Milano
Mostra sulla mappa
2825 182 Caparica
Mostra sulla mappa
75252 PARIS
Mostra sulla mappa
93420 VILLEPINTE
Mostra sulla mappa
48008 BILBAO
Mostra sulla mappa
1165 Kobenhavn
Mostra sulla mappa
41013 Sevilla
Mostra sulla mappa