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NANOPARTICLES FOR THERAPY AND DIAGNOSIS OF ALZHEIMER DISEASE

NAD

Start Date
End Date
Total Funding
€ 14 365 090
Funding Programme

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.

Project partners

Universite Pierre Et Marie Curie - Paris 6
Universiteit Antwerpen
Stab Vida Investigacao E Servicos Em Ciencias Biologicas Lda
Bial Industrial Farmaceutica S.A.
Istituto Di Ricerche Farmacologiche Mario Negri
Universite Paris-Sud
Kobenhavns Universitet
Guerbet Sa
Biotalentum Tudasfejleszto Kft
University Of Lancaster
Karolinska Institutet
Centro De Investigacion Biomedica En Red Enfermedades Neurodegenerativas
Academisch Medisch Centrum Bij De Universiteit Van Amsterdam
Universidad Del Pais Vasco/ Euskal Herriko Unibertsitatea
Turun Yliopisto
Panepistimio Patron
Nanovector Srl
Chemicky Ustav Slovenskej Akademievied
Universita' Degli Studi Di Milano-Bicocca

 
Acknowledgement
Alzheimer Europe's database on research projects was developed as part of the 2020 Work Plan which received funding under an operating grant from the European Union’s Health Programme (2014–2020).