Project description
Combining genetics and imaging for AD drug discovery
Clinical trials on new drugs against Alzheimer's disease (AD) have failed to show any efficacy in slowing disease progression, underscoring the importance of new therapeutic targets. Towards this goal, the EU-funded MAP-AD project will use autosomal and X chromosome genetic variants to identify novel molecular pathways and putative therapeutic targets. Scientists will decipher the impact of specific genetic variants on gene expression through the analysis of post-mortem brain tissue. Combined with multimodal brain imaging analysis, the genomics information will be applied to correctly enrol patients in clinical trials expediting the development of drugs for the prevention and treatment of AD.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- natural sciencesbiological sciencesgenetics
- medical and health sciencesbasic medicineneurologydementiaalzheimer
- natural sciencescomputer and information sciencesdata sciencebig data
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
75013 Paris
France