Engineered Brain Cells Show Promise as Single-Injection Alzheimer's Treatment

Washington University School of Medicine in St. Louis researchers have developed a cellular immunotherapy that could potentially treat Alzheimer's disease with a single injection — instead of the monthly infusions required by current antibody drugs.

The experimental treatment engineers astrocytes, abundant support cells in the brain, to recognize and clear amyloid beta plaques — the sticky protein deposits that accumulate in Alzheimer's patients. In mouse studies, a single injection prevented plaque formation when given early, and reduced existing plaques by about half, according to findings published in Science.

"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 senior author Marco Colonna, MD, professor of pathology at WashU Medicine.

The approach borrows from CAR-T cell cancer therapies, which genetically modify immune cells to attack tumors. Here, researchers used an adeno-associated virus to deliver a chimeric antigen receptor (CAR) into astrocytes, transforming them into what Colonna calls "super cleaners" that engulf and remove amyloid.

Current monoclonal antibody treatments for Alzheimer's require infusions once or twice monthly and have been shown to extend independent living by roughly 10 months. The new approach aims to provide a longer-lasting solution by reprogramming the brain's own cells to continuously clear toxic proteins.

"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," Colonna said.