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- W4220790014 abstract "Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common type of dementia. With no disease-curing drugs available and an ever-growing AD-related healthcare burden, novel approaches for identifying therapies are needed. In this work, we propose stage-specific candidate repurposed drugs against AD by using a novel network-based method for drug repurposing against different stages of AD severity. For each AD stage, this approach a) ranks the candidate repurposed drugs based on a novel network-based score emerging from the weighted sum of connections in a network resembling the structural similarity with failed, approved or currently ongoing drugs b) re-ranks the candidate drugs based on functional, structural and a priori information according to a recently developed method by our group and c) checks and re-ranks for permeability through the Blood Brain Barrier (BBB). Overall, we propose for further experimental validation 10 candidate repurposed drugs for each AD stage comprising a set of 26 elite candidate repurposed drugs due to overlaps between the three AD stages. We applied our methodology in a retrospective way on the known clinical trial drugs till 2016 and we show that we were able to highly rank a drug that did enter clinical trials in the following year. We expect that our proposed network-based drug-repurposing methodology will serve as a paradigm for application for ranking candidate repurposed drugs in other brain diseases beyond AD." @default.
- W4220790014 created "2022-04-03" @default.
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- W4220790014 date "2022-01-01" @default.
- W4220790014 modified "2023-10-02" @default.
- W4220790014 title "Network-based stage-specific drug repurposing for Alzheimer’s disease" @default.
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- W4220790014 doi "https://doi.org/10.1016/j.csbj.2022.03.013" @default.
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