Data-driven discovery of cell-type-directed network-correcting combination therapy for Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by heterogeneous molecular changes across diverse cell types, posing significant challenges for treatment development. To address this, we introduced a cell-type-specific, multi-target drug discovery strategy grounded in human data and real-world evidence. This approach integrates single-cell transcriptomics, drug perturbation databases, and clinical records. Using this framework, letrozole and irinotecan were identified as a potential combination therapy, each targeting AD-related gene expression changes in neurons and glial cells, respectively. In an AD mouse model, this combination therapy significantly improved memory function and reduced AD-related pathologies compared to vehicle and single-drug trea

SUBMITTER: Li Y 

PROVIDER: S-EPMC11661161 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature