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Exploitation of innovative targets against alzheimer's disease and related neurodegenerative disorders

The mission of the consortium is to implement a rational drug discovery approach to develop innovative platform of technologies, therapeutic and prophylactic strategies for the prevention and/or treatment of alzheimer's disease and related neurodegenerative disorders.

Aggregation of misfolded proteins is the hallmark of neurodegenerative disorders such as Alzheimer’s disease (AD). Currently untreatable beyond late stage symptomatic therapy, this invariably progressive disorder is increasing in prevalence (presently 45 million people worldwide) and have enormous impact on healthcare systems (the total healthcare burden for AD in the EU currently exceeds 125 billion Euros yearly). Since symptomatic treatment for AD is unlikely, prevention is the only feasible option. Established scientific evidence proves that aggregates of misfolded proteins, such as amyloid-β (Aβ) and tau are among the major molecular culprits to induce neurodegeneration in AD. A thorough understanding of molecular mechanisms driving the propagation of oligomeric and/or fibrillar aggregates would facilitate the identification of novel leads for the development of innovative disease modifying therapies against AD, but also in related neurodegenerative disorders like Parkinson's disease (PD). To meet the challenge of identifing novel anti-aggregation agents for future AD therapies, an international consortium of scientists has been formed. The primary objective of their project named XploitAD is to uncover and block fundamental mechanisms driving protein aggregation in AD. XploitAD will pursue these objectives with rational drug discovery approaches including i) advanced in silico platform for design and screening of highly selective peptide and small molecular inhibitors of protein misfolding; ii) unique preclinical models of Aβ and tau pathology. Members of the consortium have significant know-how to drive the translation of novel findings towards marketable products, technologies and services. By participating in the EU's largest drug discovery program, the Innovative Medicines Initiative (IMI), Pharmacoidea (PHI) has been exploring novel cellular pathways and membrance receptors, responsible for the cellular spreading and seeding pathological protein aggregates, including Aβ and tau. Moreover, PHI has been also screening phytochemicals capable of eliminating pathological Aβ plaques. Meanwhile Dr. Milac from the Institute of Biochemistry of the Romanian Academy (IBRA) has been applying a novel in silico methods to for the identification of new drug leads, while NANOM MEMS SRL (NNM) have been developing innovative technologies for chemical and biochemical syntheses, extraction, micro and nanofluidics, micro and nanosystems. By combining these technologies, the goal of the consortium is to discover new leads against pathological protein aggregation and exploit them as either new therapeutic candidates or specialty health foods/nutraceuticals. The consortium has disposal of scientific methodologies that can validate efficacy of the discovered leads. Along with the already established platform of assys, a prototype microfluidic system will also be developed to study protein aggregation. Druggability and therapeutic potential of newly identified agents will be broadly characterized, providing solid pre-clinical proof-of-concept for future clinical trials. Safety/efficacy validation will be supported by advanced bioinformatics. Systematic screening of the patent literature will occur in parallel to the druggability assessment in order to gain an overview on the freedom-to-operate for a given compound. In order to develop targeted delivery strategies for macromolecules, especially peptides, the synthesis of novel nanocarriers will be conducted. As botanicals are rich sources of novel anti-aggregation agents, emphasis will be put on natural compounds. Supercritical fluid extraction will be also utilized to derive natural compounds. Natural agents proven to be efficient in the rigorous scientific studies will be formulated into synergistic blends, ready to be commercialized as mental health enhancing nutratherapeutics and/or health food products. Health effects of such food products will be monitored among affected elderly. By incorporating scientifically validated, yet safe anti-aggregation natural compounds into the daily diet, the consortium can proactively address neurodegeneration and enhance cognitive health and quality of life of consumers worldwide. Employing advanced IT-tools, the state-of-the-art knowledge will be recorded and associated with relevant studies. All available experimental data will be curated and assembled into a structured electronic dossier, thus facilitating the preparation of patent and clinical trial applications along with the authorization of new health claims. Through safety/efficacy characterization, the underlying preclinical drug discovery/validation platform (including target-specific bioassays and analytical methods) will be also advanced. All will strengthen the SME’s industrial capacities and competitiveness. Dissemination of project results will increase disease awareness and also broaden scientific know-how on AD and neurodegenerative disorders.
Acronym: 
XploitAD
Project ID: 
11 774
Start date: 
01-04-2018
Project Duration: 
36months
Project costs: 
470 000.00€
Technological Area: 
Pharmaceutical Products / Drugs
Market Area: 

Raising the productivity and competitiveness of European businesses through technology. Boosting national economies on the international market, and strengthening the basis for sustainable prosperity and employment.