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A novel immunotherapy approach is showing promise in the fight against Alzheimer’s disease, with researchers successfully engineering brain cells to clear the amyloid plaques that contribute to the condition. This development offers a potential new avenue for treating a disease that currently has limited therapeutic options.
WashU Medicine Develops Immunotherapy Using CAR-Astrocytes for Alzheimer’s
Scientists at Washington University School of Medicine in St. Louis (WashU Medicine) have developed an immunotherapy that prompts brain cells called astrocytes to remove amyloid plaques, the hallmark of Alzheimer’s disease. The therapy, tested successfully in mice, involves a single injection that prevented the formation of these plaques and the resulting cognitive decline.
In mice that already had existing plaques, the injection reduced their numbers by 50%, according to a study published in Science.
The team equipped astrocytes with a CAR (chimeric antigen receptor) targeting device, enabling them to bind to and destroy the amyloid plaques. This effectively “reprograms” the astrocytes, transforming them into “super-cleaners” of the proteins that accumulate in the brain and damage neurons.
“While much operate remains to optimize this approach and address potential side effects, these results open an exciting new opportunity to turn CAR-astrocytes into an immunotherapy for neurodegenerative diseases and even brain tumors,” said lead author Marco Colonna, professor of Pathology at WashU Medicine.
How it Works and Results in Animal Models
New Alzheimer’s drugs – the first to demonstrate a change in the disease’s course – typically extend independent living by around ten months. These medications, known as monoclonal antibodies, reduce amyloid protein buildup in the brain but require frequent and high doses (once or twice monthly) to slow cognitive decline, which initially affects memory and later impacts language, reasoning, and orientation.
Alzheimer’s disease arises when a protein called beta-amyloid accumulates into plaques in the brain. Microglia, the brain’s immune cells, are responsible for clearing brain waste, but they can develop into overwhelmed in neurodegenerative diseases, hindering their ability to function effectively.
To reduce the burden on microglia, first author Yun Chen inserted a genetic targeting device into astrocytes, converting them into “super-cleaning” cells capable of eliminating harmful proteins.
Mice carrying genetic mutations that increase the risk of Alzheimer’s in humans develop beta-amyloid plaques that saturate the brain by six months of age. Chen injected a virus carrying the gene that expresses the CAR into a group of young mice without plaques and another group of older mice with plaque-saturated brains, then waited three months.
In the young mice treated before developing the disease, the injection completely prevented plaque formation. In the older mice with saturated brains, the treatment achieved a 50% reduction in plaque number within just three months.
Future and Potential Applications of the Immunotherapy
Researchers have filed a patent for the approach used to design the CAR-astrocytes.
“This new CAR-astrocyt immunotherapy is most effective when administered in the early stages of the disease,” emphasized co-author David Holtzman. However, he added, “what differentiates it and could make a difference in clinical care is the single injection that successfully reduced the amount of damaging brain proteins in mice.”
The team plans to further refine this immunotherapy and adjust its design to better target harmful proteins without negatively impacting the normal functions of brain cells. They similarly believe that by modifying the CAR targeting device to enable astrocytes to recognize specific markers on brain tumors, these cells could be harnessed to eliminate tumor cells, potentially offering a new and promising approach to brain cancer and other central nervous system diseases.
