Advanced Patient-Derived Microglia Assay for Preclinical and Clinical Trial Drug Validation
Abstract
In this proposal, we are investigating the potential of a new model system to culture microglia from people with ALS and demonstrate that this model is ideal for patient pre-selection for clinical trials, and for ongoing monitoring of drug action during trials. The model involves preparation of microglia directly from cells in the blood called monocytes. The presence of pathological changes in ALS monocyte-derived microglia provides us with the unique opportunity to determine if drugs are able to induce normal outcomes in these cells, and therefore, more likely improve function in people with ALS. The initial aim is to benchmark monocyte-derived microglia against other microglia commonly used for drug screening (iPSC-derived microglia, and mouse SOD1 ALS model microglia). The annual report predominantly covers this aim, and preparations for the subsequent aims of demonstrating that patient monocyte-derived microglia provide a clinically relevant platform for assessment of ALS drug efficacy and demonstrating that patient microglia TDP-43 aggregation and phagocytosis are qualifiable biomarkers for microglia-targeted drug development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2023
- Accession Number
- AD1212567
Entities
People
- Anthony White
Organizations
- QIMR Berghofer Medical Research Institute