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A multimodal approach to accelerate drug discovery and development in Alzheimer’s disease

Descrizione del progetto

Combinazione di genetica e imaging per la scoperta di farmaci per il morbo di Alzheimer

Gli studi clinici su nuovi farmaci contro il morbo di Alzheimer non sono riusciti a dimostrare alcuna efficacia nel rallentare la progressione della malattia, sottolineando l’importanza di nuovi bersagli terapeutici. Per far questo, il progetto MAP-AD, finanziato dall’UE, utilizzerà varianti genetiche autosomiche e del cromosoma X per identificare nuovi percorsi molecolari e presunti bersagli terapeutici. Gli scienziati decifreranno l’impatto di specifiche varianti genetiche sull’espressione genica attraverso l’analisi del tessuto cerebrale post mortem. In combinazione con un’analisi multimodale di imaging cerebrale, saranno applicate informazioni di genomica per arruolare correttamente i pazienti negli studi clinici accelerando lo sviluppo di farmaci per la prevenzione e il trattamento del morbo di Alzheimer.

Obiettivo

Alzheimer’s disease (AD) is a major societal challenge, impacting up to one third of the population over 85 years old. The European Commission and various international bodies have repeatedly fostered research initiatives to prevent the development or stem the progression of the disease. Several recent phase 3 clinical trials have failed to show any efficacy in slowing disease progression, calling into question the current drug targets. This project will use genetic data to identify new AD-relevant molecular pathways and their associated drug targets. Given the increased risk of AD in women, we will apply our innovative analyses not only to autosomal variants but also to X-chromosome variants as well. The mechanistic effects of genetic variants on pathogenesis will be delineated using gene expression from post-mortem brain tissue and AD biomarkers derived from multimodal brain imaging studies. These in-vivo PET and MRI biomarkers are essential for enrolling patients correctly in clinical trials and assessing the effect of treatments on disease progression. We will assess whether a polygenic risk score, based on thousands of genetic variants, will be useful in predicting an individual’s clinical and biomarker progression over time. This project is markedly interdisciplinary in nature between its analysis of multimodal brain imaging and genomics data, and the combination of big data analysis guided by expert medical knowledge of the pathogenesis. Results have the potential to (i) identify new drug targets and (ii) strengthen clinical trial design, thereby speeding the development of drugs for the prevention and treatment of AD. This fellowship represents a unique opportunity to transfer knowledge and analysis methods of next generation genomics AD data from one of the leading US groups in integrating multimodal imaging and genomics data to the European AD research community.

Parole chiave

Coordinatore

INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE
Contribution nette de l'UE
€ 257 619,84
Indirizzo
BOULEVARD DE L'HOPITAL 47
75013 Paris
Francia

Mostra sulla mappa

Regione
Ile-de-France Ile-de-France Paris
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 257 619,84

Partner (1)