An integrated platform for the single-cell transcriptomics-based identification of repurposable therapeutics in Alzheimer’s Disease (AD) using human iPSCs-derived 3D neuroimmune co-cultures

• Applicant: Dr. Caterina Carraro
• Subject Area: Experimental Models for the Understanding of Nervous System Diseases
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554365317

Dementia represents a pressing social burden with a prevalence expected to increase from 55.2 million patients in 2019 to 139 million by 2050 worldwide. Among dementias, Alzheimer’s Disease (AD) is the most common form, contributing to 60% of all reported cases. While the approval of novel biologics has been a breakthrough in AD therapy, the observation that only a subset of AD patients seems to benefit points towards the need for additional therapeutic options. Consequently, there is a pressing need to develop novel therapeutic agents to be included into multi-target treatment strategies and to address the need for patient stratification based on the observed heterogeneous clinical manifestations of the dementias. For their inherent systems-level readouts, omics technologies can complement reductionists approaches capturing novel aspects of AD disease complexity, pointing toward alternative therapeutic avenues. Besides, repurposing of existing drugs represents an attractive yet underexplored option in early drug discovery to speed up the identification of novel therapeutics for AD, especially when combined with high-dimensional omics technologies and the use of novel advanced in vitro models able to capture the brain cellular heterogeneity. In this direction, the overall aim of my project is to establish an end-to-end omics workflow for the repurposing of therapeutic agents for AD based on a human iPSCs-derived 3D neuroimmune co-culture model. I will first identify promising cell type-specific drugs in silico and then test them in vitro using single-cell transcriptomics to screen for the most promising agents. Further, I will exploit the obtained omics information to predict effective multi-target treatment combinations and test them in vitro, concluding with the validation of obtained findings using a set of complementary experimental approaches.

• DFG Programme: WBP Position