Delivery Courier? Microglia Drop Neprilysin Off Near Plaques in Brain
The blood-brain barrier border protects the brain by regulating the flow of molecules, peptides, and cells, but it also keeps out many therapeutics. Now, researchers have harnessed the power of a resident drug courier, i.e., microglia.
-
Researchers genetically engineered human iPSC-microglia to deliver neprilysin when the cells are near amyloid plaques.
- Both local injection and brain-wide engraftment of neprilysin-secreting microglia reduced Aβ pathology.
- Only widespread engraftment helped reduce pathologies and improve neuronal density in the subiculum.
Mathew Blurton-Jones and his team at the University of California, Irvine, have engineered human iPSC-derived microglia (iMG) to ferry protein therapeutics into the brain. They CRISPR-engineered the immune cells to express the Aβ-degrading enzyme neprilysin, but only in areas where the cells encounter amyloid plaques. When the researchers injected the couriers into mouse models of Alzheimer’s disease, the cells not only reduced the amount of amyloid, but also improved downstream aspects of Alzheimer’s pathogenesis. “While there are, of course, other approaches to reduce [Aβ] levels, this study demonstrated the powerful potential of iPSC-microglia to provide a novel immune cell therapy for a broad array of neurological diseases,” senior author Blurton-Jones wrote to Alzforum.
Read the full article here.
