Image Courtesy: Machairaki lab
Scientists have grown miniature brain-like tissues from the cells of Alzheimer’s patients and found they may help predict how individual patients respond to certain medications, potentially opening a new path toward more personalized treatment.
Researchers at Johns Hopkins Medicine created hundreds of pea-sized brain organoids from patient cells and exposed them to escitalopram, a commonly prescribed antidepressant. Some showed strong molecular responses to the drug, while others showed little or no change, suggesting the models could eventually identify groups of patients more likely to benefit from particular treatments.
The study focused on psychiatric symptoms associated with Alzheimer’s disease, which affects more than 7 million Americans. While there is no cure for Alzheimer’s, selective serotonin reuptake inhibitors, or SSRIs, are frequently prescribed to manage symptoms including depression, anxiety, and agitation. Patients can respond very differently to these medications.
Researchers began with blood samples from Alzheimer’s patients and reprogrammed the cells into induced pluripotent stem cells, which can develop into different cell types. They then guided these cells into organoids resembling the hindbrain, including neurons capable of producing serotonin.
The Alzheimer’s-derived organoids reproduced several molecular characteristics associated with the disease. Compared with organoids from healthy participants, they showed differences in proteins connected to inflammation, neuronal communication, and Alzheimer’s-related biological pathways.
When treated with escitalopram, some patient-derived organoids showed increases in proteins involved in serotonin signaling and communication between neurons. Others barely responded.
“Our model may eventually be used to identify subgroups of patients, based on underlying molecular mechanisms, who are more likely to respond to certain drugs,” said study leader Vasiliki Machairaki of the Johns Hopkins University School of Medicine.
Researchers also analyzed extracellular vesicles, tiny particles released by cells that carry molecular information. Vesicles from Alzheimer’s organoids showed altered levels of several proteins, including RAB3A, NSF, and ATCAY. Some of these molecular signatures changed following treatment.
The team hopes these vesicles could eventually contribute to a “liquid biopsy” capable of helping diagnose Alzheimer’s, determine its stage, or predict treatment response. Researchers caution, however, that the work remains at an early experimental stage.
