A team at the University of California, Irvine has developed a novel method to potentially improve treatment for Alzheimer’s disease and other neurological disorders. By engineering human microglia, the researchers have created cellular vehicles capable of targeting brain pathology and releasing therapeutic agents where necessary. The research, supported by grants from various organizations and published in Cell Stem Cell, explored how these modified microglia can detect changes in the brain and respond accordingly. They successfully demonstrated that microglia derived from induced pluripotent stem cells can be programmed to release enzymes that degrade toxic proteins such as amyloid plaques found in Alzheimer’s.
“Delivering biologics to the brain has long been a major challenge because of the blood-brain barrier,” said Mathew Blurton-Jones, UC Irvine professor of neurobiology and behavior and co-corresponding author on the study. The study shows that engineered microglia can reduce brain inflammation, preserve neurons, and reverse signs of neurodegeneration in mice. This could represent a significant step forward for patients suffering from Alzheimer’s and related conditions.
Using CRISPR gene editing, the modified microglia secrete neprilysin, an enzyme that degrades beta-amyloid, leading to a highly targeted response. As a result, inflammation and neuronal damage were reduced in mouse models.
Jean Paul Chadarevian, a postdoctoral scholar and first author on the study, noted the approach’s success in different brain areas, explaining how the targeted yet broad effectiveness was achieved. The research also explored engineered microglia’s response in brain cancer and multiple sclerosis models, underscoring the potential for tailored treatments for a range of conditions.
“This work opens the door to a completely new class of brain therapies,” said Robert Spitale, UC Irvine professor of pharmaceutical sciences and co-corresponding author. While challenges remain, such as ensuring long-term safety and developing scalable production methods, the study offers hope for a new generation of brain disease therapies.
The University of California, Irvine, founded in 1965, is ranked among the nation’s top public universities and plays a significant role in academic research. With over 36,000 students, the campus contributes significantly to the local economy and is known for its innovation.
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