A groundbreaking study published on , offers a potential new avenue for treating Alzheimer’s disease, a neurodegenerative condition affecting millions worldwide. Researchers have discovered that two existing, FDA-approved cancer drugs show promise in reversing some of the damage caused by the disease, offering a glimmer of hope after years of limited treatment options.
The research, conducted by teams at the University of California San Francisco (UCSF) and the Gladstone Institutes, began with a detailed analysis of how Alzheimer’s disease alters gene expression within individual brain cells. Scientists sought to identify drugs already approved for other conditions that could counteract these changes, specifically targeting neurons and glial cells – both of which are impacted by the disease. The team analyzed millions of electronic medical records to identify patients who had taken these drugs as part of their cancer treatment and then compared their incidence of Alzheimer’s disease to those who hadn’t.
The investigation pinpointed two cancer medications – letrozole and irinotecan – as potential candidates. Letrozole is commonly used to treat breast cancer, while irinotecan is used for colon and lung cancers. When tested in combination on a mouse model of Alzheimer’s disease, the drugs not only reduced brain degeneration but also restored some cognitive function, specifically the ability to remember.
“Alzheimer’s disease comes with complex changes to the brain, which has made it tough to study and treat, but our computational tools opened up the possibility of tackling the complexity directly,” explained Marina Sirota, PhD, interim director of the UCSF Bakar Computational Health Sciences Institute and professor of pediatrics, in a statement accompanying the study’s release.
The underlying mechanism appears to involve reversing the gene expression changes characteristic of Alzheimer’s. The disease is known to cause the accumulation of amyloid plaques and tau protein tangles in the brain, leading to inflammation and neuronal damage. The study suggests these drugs may help reduce these pathological hallmarks. Researchers observed a reduction in tau protein clumps in the brains of the treated mice, a key indicator of disease progression.
This approach represents a significant shift in Alzheimer’s research. Traditionally, drug development has focused on targeting amyloid plaques directly. This new strategy, however, focuses on restoring the brain’s natural cellular processes and reducing inflammation. The researchers emphasize that Here’s not a cure, but a potential way to slow or even reverse some of the disease’s debilitating effects.
The findings build upon earlier work by Professor Zelig Eshhar of the Weizmann Institute of Science, whose pioneering research in the 1990s laid the foundation for CAR-T cell therapy – a type of immunotherapy now used to treat certain cancers. The principle of genetically engineering immune cells to target specific molecules in the body has now been extended to address the challenges of Alzheimer’s disease.
A related study, led by researchers at the Weizmann Institute of Science and Washington University in St. Louis, took this concept a step further, utilizing CAR-T cell therapy directly in a mouse model of Alzheimer’s. In this approach, immune cells were modified to recognize and respond to amyloid proteins in the brain, leading to a reduction in amyloid deposits and inflammation. This represents the first application of CAR-T cell therapy to a neurodegenerative disease.
“We are presenting the first CAR-T approach for a neurodegenerative disease,” stated Jonathan Kipnis, MD, of the Weizmann Institute. “This is an exciting step toward discovering new therapies for Alzheimer’s. Equally exciting is the possibility of adapting these versatile cells to deliver therapeutic agents for different neurodegenerative diseases beyond Alzheimer’s, such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease.”
The World Health Organization (WHO) estimates that over 55 million people globally live with dementia, with Alzheimer’s disease being the most common form. This number is projected to rise dramatically in the coming decades as the global population ages, underscoring the urgent need for effective treatments.
While these findings are promising, it’s crucial to remember that the research is still in its early stages. The studies were conducted on mouse models, and further research is needed to determine whether these drugs will be safe and effective in humans. Clinical trials will be necessary to assess the potential benefits and risks of this approach. However, the identification of these existing drugs as potential Alzheimer’s treatments offers a significant advantage, as they have already undergone extensive safety testing for their approved uses.
Researchers are optimistic that this new approach could pave the way for a new generation of therapies for Alzheimer’s disease and other neurodegenerative conditions, offering hope to patients and families affected by these devastating illnesses.
