Breakthrough in Alzheimer’s Treatment Using Blood Cancer Therapy
An international research team, with leaders from the Weizmann Institute of Science and Washington University School of Medicine in St. Louis, has made a notable advancement. They’ve adapted a form of immunotherapy, specifically for blood cancers, to potentially combat Alzheimer’s disease.
This innovative approach, known as CAR T-cell therapy, has shown promising results in mouse models of Alzheimer’s. If successful in broader applications, it could open doors for new treatments for this devastating brain disorder and other related neurodegenerative diseases.
The detailed study, which underwent peer review, was released on Monday in the Proceedings of the National Academy of Sciences. It was spearheaded by Prof. Ido Amit from Weizmann’s Systems Immunology Department, alongside Prof. Jonathan Kipnis from Washington University, with significant contributions from postdoctoral fellow Dr. Pavle Boskovic.
The foundational work for this research can be traced back over 30 years to Prof. Zelig Eshhar, a recipient of the Israel Prize, who developed CAR-T therapy. Eshhar passed away last July, yet his groundbreaking ideas live on. “His remarkable innovation was initially intended for blood cancer, but we realized it could be applied more widely,” Amit mentioned in a discussion.
In Israel alone, around 150,000 individuals are estimated to be living with Alzheimer’s and various neurodegenerative illnesses. The roots of Alzheimer’s still remain quite unclear, though a key characteristic is the clustering of amyloid-beta protein plaques in the brain, which corresponds with inflammation in the surrounding tissue.
These amyloid plaques damage nerve cells, contributing to the decline in cognitive abilities and memory loss characteristic of Alzheimer’s.
Eshhar’s Legacy and the CAR-T Approach
The research team focused on isolating T cells from healthy mice. These T cells, or T lymphocytes, are critical white blood cells that aid the immune system in its battle against infections and diseases. However, they are typically insufficient for fighting cancer.
Eshhar was pioneering in extracting T cells and genetically altering them to detect and attack cancer cells effectively. “This approach was quite unexpected—it’s like how Israel innovated cherry tomatoes. Instead of merely crafting antibodies or drugs, he engineered cells to act as the drug,” noted Amit.
Building on Eshhar’s discoveries, the Alzheimer’s research team modified these T cells to recognize amyloid proteins present in the brain.
The researchers then administered these enhanced cells into mice already displaying amyloid-beta plaques. This led to a marked decrease in plaque accumulation and reduced inflammation in the brain’s tissue.
The innovative combination of genetics, big data, machine learning, as well as what Amit describes as “synthetic biology and synthetic immunology,” allowed the engineered T cells to target the problematic brain areas effectively, with the aim to interrupt the damaging cycle caused by Alzheimer’s.
Kipnis, who received his PhD from Weizmann, expressed that this marks the first application of CAR T-cell therapy for a neurodegenerative illness.
“This is a novel and exciting opportunity for developing therapies for Alzheimer’s and other significant neurodegenerative conditions like ALS and Parkinson’s,” he commented.
Amit emphasized that Eshhar’s contribution continues to inspire creativity in research directions at Weizmann. The team plans to expand on this technology to explore viable methods for delivering various growth factors that might aid in recovery from severe brain injuries and possibly even foster the regeneration of brain tissue.
