NAD

NANOPARTICLES FOR THERAPY AND DIAGNOSIS OF ALZHEIMER DISEASE

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 Obiettivo del progetto (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.'

Introduzione (Teaser)

Tiny warriors fight Alzheimer's

Descrizione progetto (Article)

Dementia affects more than 24 million people globally with one new case diagnosed every seven seconds. Three million of the 5 million cases in Europe are classified as AD, the most common form of dementia. As the aging population continues to grow, the numbers are expected to rise dramatically.

Amyloid deposits in the brain are characteristic of AD but treatment is ironically complicated by the protective-in-function blood - brain barrier. This barrier has prevented the use of simple oral or nasal interventions to deliver drugs through the blood to the targeted area in the brain.

EU-funded scientists working on the project 'Nanoparticles for therapy and diagnosis of Alzheimer Disease' (http://www.nadproject.eu (NAD)) exploited nanoparticles to do the job. Their very small size imparts powerful functionalities to nanoparticles such as enhanced contrast during imaging procedures and crossing the blood - brain barrier. NAD functionalised a variety of nanoparticles including liposomes, solid lipid nanoparticles and polymeric nanoparticles.

Through positron emission tomography and magnetic resonance imaging, researchers' demonstrated that these nanoparticles could disaggregate and remove amyloid deposits, restoring impaired memory in animal models. The amazing success of the multi-functionalised nanoparticles of various types has been recognised internationally.

The project won second place in the 'Best Completed Project Contest' with the award presented by the Director responsible for Research and Innovation in the European Commission. Outcomes resulted in more than 50 publications in international peer-reviewed scientific journals and four international patent applications.

Demonstrated combined diagnosis and therapy of AD with orally or nasally administered nanoparticles is an exceptional advance in the war against a devastating disease. This technique opens the door for treatment of other central nervous system disorders through nanoparticle-based diagnostics for an even broader spectrum of diseases. This will enhance the quality of life for millions of patients and their families through better health while dramatically increasing EU industrial competitiveness.