Researchers at Washington University School of Medicine in St. Louis have developed a new cellular immunotherapy that targets amyloid plaques associated with Alzheimer's disease. The therapy, which uses engineered brain cells known as astrocytes equipped with a chimeric antigen receptor (CAR), requires only a single injection in mice.
The study, published March 5 in Science, shows that when administered before the onset of amyloid plaque formation, the treatment prevents plaques from developing. In mice that already had plaque buildup, a single dose cut the amount of amyloid plaques by half.
"This study marks the first successful attempt at engineering astrocytes to specifically target and remove amyloid beta plaques in the brains of mice with Alzheimer's disease," said Marco Colonna, MD, senior author and Robert Rock Belliveau, MD, Professor of Pathology at WashU Medicine. "Although more work needs to be done to optimize the approach and address potential side effects, these results open up an exciting new opportunity to develop CAR-astrocytes into an immunotherapy for neurodegenerative diseases and even brain tumors."
Current monoclonal antibody drugs for Alzheimer's require regular infusions every few weeks and can extend independent living by about 10 months. The new CAR-astrocyte therapy aims to reduce treatment frequency while improving effectiveness.
First author Yun Chen, PhD, developed the method during his graduate studies at Washington University by delivering a gene encoding the CAR into astrocytes using a harmless virus injected into mice. This enabled astrocytes—the most common cell type in the brain—to capture and remove amyloid beta proteins more efficiently.
In tests involving genetically modified mice prone to developing Alzheimer's-like symptoms, younger animals treated before plaque development showed no signs of plaque accumulation after six months. Older mice with existing plaques experienced a 50% reduction compared to controls.
"Consistent with the antibody drug treatments, this new CAR-astrocyte immunotherapy is more effective when given in the earlier stages of the disease," said David M. Holtzman, MD, co-author on the paper and Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology at WashU Medicine. "But where it differs, and where it could make a difference in clinical care, is in the single injection that successfully reduced the amount of harmful brain proteins in mice."
The research team has filed a patent for their approach with assistance from Washington University's Office of Technology Management.
Looking ahead, researchers plan to further refine their therapy to better target harmful proteins without affecting normal brain functions. They also see potential for adapting this technique so astrocytes could recognize markers on brain tumors and help eliminate them—expanding possible applications beyond Alzheimer’s disease.
