Hindbrain organoids for drug screening for the treatment of neuropsychiatric symptoms in Alzheimer's disease
2024
Johns Hopkins School of Medicine, Baltimore, USA
Almost all Alzheimer's disease (AD) patients suffer from neuropsychiatric symptoms (NPS), the emergence of which correlates with dysfunctional serotonergic systems. In this study, human peripheral blood mononuclear cells (PBMCs) from healthy volunteers and AD patient with or without NPS were reprogrammed into iPSCs and subsequently differentiated into hindbrain organoids. The presence of serotonergic neurons was confirmed by quantitative reverse transcription PCR, flow cytometry, immunocytochemistry, and detection of released serotonin (5-HT). To assess patient-specific treatment effects, organoids were treated with different concentrations of escitalopram oxalate, commonly prescribed for NPS. Changes in serotonin levels before and after treatment with escitalopram were dose-dependent and variable across patients.
The authors propose that this 3D platform might be effectively used for drug screening purposes to predict patients with NPS most likely to respond to treatment in vivo and to understand the heterogeneity of treatment responses.
iPSC-derived hindbrain organoids to evaluate escitalopram oxalate treatment responses targeting neuropsychiatric symptoms in Alzheimer’s disease
Vasiliki Mahairaki
Added on: 12-10-2024
[1] https://www.nature.com/articles/s41380-024-02629-y
