The recent publication in the journal Brain Communications uses a cell morphology-based imaging assay to classify hits in a pilot drug screen on a human neural progenitor cell model of Alzheimer’s disease: April 2024 Image Dr Kathy Evans and Dr Amina McDiarmid Alzheimer’s disease, the most common form of dementia, affects huge numbers of people worldwide. While some advances have been made recently, treatments remain inadequate and new approaches to drug discovery are greatly needed. Genetic, clinical and functional analyses strongly support involvement of the sortilin-related receptor 1 (SORL1) gene which encodes the protein SORLA in Alzheimer’s disease. A new paper from Dr Kathy Evans research group describes how first author, Dr Amina McDiarmid, used loss of SORL1 to model Alzheimer’s disease in neural progenitor cells, and tested whether cell painting, an automated imaging assay that assesses cell phenotype that has been previously used in drug discovery for cancer, could be applied to Alzheimer’s disease. Morphological profiles generated by this assay were used to identify cellular features characteristic of SORL1 deletion and to determine the phenotypic response of neural progenitor cells lacking this protein to treatment with compounds from a small drug repurposing library. This identified 14 drugs that caused reversion of the mutant morphological signatures towards those of control neural progenitor cells. The work suggests that phenotypic screening combined with high-content image analysis is a viable option for drug repurposing and discovery in this human neural cell model of Alzheimer’s disease. Click here to read to the article (external link) This proof-of-principal study is exciting, as it indicates that in the future it may be possible to use morphological profiling in the identification of candidate therapeutics for Alzheimer’s disease. Dr Kathy Evans Links Kathy Evans Research Group This article was published on 2024-06-21
