Alzheimer’s Breakthrough: Cancer Therapy Repurposed to Fight Neurodegeneration
In a groundbreaking development, researchers from the Weizmann Institute of Science and Washington University School of Medicine in St. Louis have successfully repurposed a cancer immunotherapy – CAR T-cell therapy – to combat Alzheimer’s disease in a mouse model. This innovative approach, detailed in a study published in the Proceedings of the National Academy of Sciences, offers a potential new avenue for treating this devastating neurodegenerative disorder.
The Legacy of Prof. Zelig Eshhar and CAR-T Technology
The research builds upon the pioneering work of the late Professor Zelig Eshhar of the Weizmann Institute, who developed CAR-T (Chimeric Antigen Receptor T-cell) therapy over 30 years ago. Originally designed to target and destroy cancer cells, CAR-T therapy involves genetically engineering a patient’s own T cells – white blood cells crucial for immune function – to recognize and attack specific targets. Professor Eshhar’s work, described as “completely unexpected” by Prof. Ido Amit of Weizmann, involved engineering cells to *become* the drug, rather than relying on traditional antibodies or compact-molecule drugs.
The team, led by Prof. Amit and Prof. Jonathan Kipnis, adapted this technology to target amyloid-beta proteins, a hallmark of Alzheimer’s disease. They genetically engineered T cells to recognize and respond to these amyloid proteins in the brain.
How CAR T-Cells Combat Alzheimer’s in Mice
The engineered CAR T-cells were injected into mice exhibiting amyloid-beta plaque buildup, a key characteristic of Alzheimer’s. The results were promising: the injections led to a significant reduction in amyloid deposits and a decrease in markers of brain-tissue inflammation. Researchers utilized genetics, big data, machine learning, and “synthetic biology and synthetic immunology” to guide the modified T cells to the affected areas of the brain, effectively disrupting the damaging cycle.
Future Trends: Beyond Alzheimer’s and Towards Brain Regeneration
This research represents the first CAR T-cell approach for a neurodegenerative disease, according to Prof. Kipnis. However, the potential extends far beyond Alzheimer’s. Researchers envision utilizing this technology to address other neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and Parkinson’s disease.
Looking ahead, the team aims to leverage this platform to deliver “all kinds of cargo, or different growth factors, that will support recovery from severe brain damage, and even the regrowth and regeneration of brain tissue,” explains Prof. Amit. This suggests a future where immunotherapy isn’t just about clearing harmful proteins, but actively repairing and restoring damaged brain tissue.
The Role of Microglia and Monocyte-Derived Macrophages
Recent research from the Weizmann Institute, detailed in PubMed, highlights the crucial role of microglia and monocyte-derived macrophages (MDM) in Alzheimer’s disease. Studies indicate that blocking PD-L1, an immune checkpoint, can modify the disease’s progression via MDM involvement, even independently of TREM2, a protein previously thought to be essential for this process. This underscores the complexity of the immune response in Alzheimer’s and the potential for targeted immunotherapies.
WashU-Weizmann Collaboration: A Catalyst for Innovation
The collaboration between Washington University School of Medicine and the Weizmann Institute of Science, established in February 2025, is designed to foster joint research projects focused on understanding the interplay between microbes, the immune system, and the nervous system in human health and disease. This partnership provides a substantial source of seed funding for researchers, particularly early-career scientists, to develop innovative research programs.
Frequently Asked Questions (FAQ)
- What is CAR T-cell therapy?
- CAR T-cell therapy is a type of immunotherapy where a patient’s own T cells are genetically engineered to recognize and attack specific targets, like cancer cells or, in this case, amyloid-beta proteins.
- What role did Prof. Zelig Eshhar play in this research?
- Prof. Eshhar developed the foundational CAR-T technology over 30 years ago, providing the basis for this new Alzheimer’s treatment approach.
- Is this treatment available for humans yet?
- No, this research has only been conducted in a mouse model. Further research and clinical trials are needed before it can be used to treat humans.
- What is the significance of the WashU-Weizmann collaboration?
- The collaboration provides funding and resources for researchers at both institutions to work together on understanding and treating complex diseases like Alzheimer’s.
Did you know? Approximately 150,000 people in Israel are affected by Alzheimer’s and other neurodegenerative diseases.
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