Researchers have engineered astrocytes to express chimeric antigen receptors, enabling targeted clearance of amyloid-β in vitro and in mouse models, in a study published in Science.
These modified cells, dubbed CAR-expressing astrocytes, were designed to recognize and remove amyloid-β (Aβ), the protein that forms plaques widely associated with Alzheimer’s pathology.
In mouse models, engineered astrocytes enhanced Aβ clearance in vitro and, when delivered noninvasively using adeno-associated viral vectors, reduced plaque burden in the brain. Early administration also prevented Aβ accumulation and associated pathology.
Current anti-amyloid therapies, including monoclonal antibodies, require high doses and repeated administration and are associated with safety risks. In contrast, the CAR-expressing astrocytes approach is designed as a self-sustaining system that enables brain cells to recognize and clear Aβ while avoiding repeated dosing.
The study also showed that different CAR designs produced distinct biological effects, with some acting primarily on astrocytes and others additionally engaging microglia. The researchers noted that these differences reflect the flexibility of the platform and its potential to tailor CAR signaling to achieve specific therapeutic goals. Delivery using adeno-associated virus enabled widespread expression in the central nervous system.
As the findings are based on in vitro and mouse model data, further work will be needed to assess safety, delivery, and translation to humans. “As CAR technologies mature and the ability to selectively neutralize toxic proteins improves, these approaches hold substantial promise for [Alzheimer’s disease] and other neurodegenerative disorders,” noted Jake Boles and David Gate, in a press release.
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