CAR-T Cell Therapy Shows Promise for Alzheimer's Disease in First Neurodegenerative Application
Key Insights
Researchers at Washington University School of Medicine and Weizmann Institute of Science have successfully adapted CAR-T cell therapy (search), originally developed for cancer treatment, to target Alzheimer's disease (search) in mice.
The engineered CAR-T cells specifically targeted amyloid beta (search) plaques in the brain, resulting in significant plaque reduction and decreased brain inflammation compared to control treatments.
This represents the first application of CAR-T cell therapy (search) for neurodegenerative diseases and could potentially be adapted for other conditions including ALS and Parkinson's disease (search).
Researchers have achieved a significant breakthrough by successfully adapting chimeric antigen receptor (CAR) T cell therapy for Alzheimer's disease (search) treatment, marking the first application of this cancer immunotherapy approach to neurodegenerative conditions. The collaborative study between Washington University School of Medicine in St. Louis and the Weizmann Institute of Science in Israel demonstrated that engineered CAR-T cells can effectively reduce harmful amyloid beta (search) plaques in mouse brains while improving overall brain tissue health.
Novel Therapeutic Approach Targets Amyloid Plaques
The research team, led by co-senior authors Jonathan Kipnis, PhD, from Washington University and Ido Amit, PhD, from the Weizmann Institute, engineered T cells to specifically recognize and respond to amyloid proteins in the brain. CAR-T cell therapy (search), originally developed over 30 years ago for cancer treatment, genetically modifies a patient's immune cells to attack specific targets and has transformed treatment for certain blood cancers.
"We report the first CAR-T cell approach for a neurodegenerative disease. It represents an exciting step towards finding novel therapies for Alzheimer's disease (search)," said Kipnis, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology and Immunology at WashU Medicine.
Promising Preclinical Results
In the experimental protocol, first author Pavle Boskovic, PhD, a postdoctoral fellow in the Kipnis lab, extracted T cells from healthy mice and genetically modified them to target amyloid proteins. The team then injected these engineered cells into 6-month-old mice carrying genetic mutations found in Alzheimer's patients, which had developed amyloid beta (search) plaques in their brains.
The mice received three injections of either modified CAR-T cells or non-modified control cells, spaced 10 days apart. Ten days after the final injection, researchers observed a greater reduction of amyloid beta (search) plaques in brains of mice treated with engineered CAR-T cells compared to those receiving control treatments.
Improved Brain Health Markers
Beyond plaque reduction, the CAR-T cell-treated mice demonstrated healthier brain profiles compared to control groups. The treatment resulted in reduced activation of microglia and astrocytes, two types of brain cells whose excessive activation is associated with neuroinflammation. This reduction in cellular activation followed the observed plaque reduction, suggesting a comprehensive improvement in brain health.
Broader Therapeutic Potential
The researchers emphasized the versatility of this approach for treating multiple neurodegenerative conditions. Kipnis noted the "exciting prospect of adapting these versatile cells to deliver therapeutic agents for different neurodegenerative diseases beyond Alzheimer's, including amyotrophic lateral sclerosis (search) (ALS) and Parkinson's disease (search)."
The team also suggested that the same approach could potentially be adapted to treat other neurodegenerative conditions and may one day help repair brain damage caused by injury or stroke.
Future Research Directions
Looking ahead, the research team plans to investigate the mechanisms by which engineered CAR-T cells improve brain health in Alzheimer's disease (search). "We also aim to explore using them in mouse models of other neurodegenerative diseases that feature inflammation, with the hope that one day such cells can be safely and effectively used as a therapeutic to help people impacted by neurodegenerative disease," Boskovic explained.
The study, published February 9 in the Proceedings of the National Academy of Sciences (PNAS), represents Kipnis' first project funded by the Carol and Gene Ludwig Initiative in Neuroimmunology Research. The research was supported by the National Institute on Aging, the Carol and Gene Ludwig Family Foundation, and the Cure Alzheimer's Fund.