CAR-T therapy, best known for fighting blood cancers, is now being repurposed for brain disease. Researchers at Washington University in St. Louis and the Weizmann Institute of Science report that engineered T cells can reduce amyloid plaques – the toxic protein clumps linked to Alzheimer’s – in mouse models, while also improving markers of brain health.
The team designed CD4+ CAR-T cells to recognize fibrillar amyloid-beta, a key pathological hallmark of Alzheimer’s disease. After multiple injections into mice, the engineered cells accumulated at sites of pathology and significantly reduced amyloid burden compared with control treatments. The therapy also dampened activation of microglia and astrocytes – two cell types that drive neuroinflammation – suggesting broader effects on the brain’s immune environment.
“We report the first CAR-T cell approach for a neurodegenerative disease,” said co-senior author Jonathan Kipnis in a press release. “It represents an exciting step towards finding novel therapies for Alzheimer’s disease.” He added that the approach could be adapted for other conditions: “Equally exciting is the prospect of adapting these versatile cells to deliver therapeutic agents for different neurodegenerative diseases beyond Alzheimer’s.”
Importantly, the researchers also tested a transient, mRNA-based version of the therapy to avoid prolonged immune activation – a known risk with CAR-T approaches. This shorter-lived strategy not only reduced plaque load in brain tissue but also decreased microgliosis, astrogliosis, and neuronal damage markers, pointing to a potentially safer therapeutic route.
Still, the work remains at an early, preclinical stage. “We also aim to explore using them in mouse models of other neurodegenerative diseases that feature inflammation,” said first author Pavle Boskovic, “with the hope that one day such cells can be safely and effectively used as a therapeutic.”
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