Single dose of CAR-astrocyte therapy halves amyloid levels in mice brains

The new generation of Alzheimer's disease drugs - the first proven to change the course of the disease - typically extend independent living for patients by 10 months. Called monoclonal antibodies, they reduce the accumulations of a harmful protein, amyloid, in the brain and require high-dose, once- or twice-monthly infusions of the medication.

Now, to reduce the frequency of treatment and potentially improve the efficacy of an anti-amyloid therapy, researchers at Washington University School of Medicine in St. Louis have engineered a new cellular immunotherapy that requires just a single injection to prevent amyloid plaques from developing when given before plaques start to form in mice. Furthermore, a single treatment in mice that had already developed plaques cut the amount of amyloid plaques in half.

Like CAR-T cell therapies used for cancer treatment, in which T cells of the immune system are genetically modified to attack cancer cells, this new approach equips cells - in this case, brain cells called astrocytes - with a CAR homing device to grab onto a target for destruction. These new CAR-astrocyte cells have features that transform them into super cleaners that remove damaging proteins from the brain that play a role in cognitive decline.

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. 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."