In the quest to combat Alzheimer’s disease, researchers are turning to existing medications that might help. A new study has pinpointed two noteworthy candidates, both of which are currently utilized in cancer treatment.
These drugs, letrozole (primarily for breast cancer) and irinotecan (used for colon and lung cancer), have already received approval from U.S. regulators. This means that potential clinical trials for Alzheimer’s could commence relatively soon.
Researchers from the University of California, San Francisco (UCSF) and Gladstone Institutes began their investigation by examining how Alzheimer’s affects gene expression in the brain.
They analyzed a medical database called the Connectivity Map to identify drugs that could counteract these gene expression alterations and looked into patient records of those who had taken these cancer drugs, noting a potential reduction in their likelihood of developing Alzheimer’s.
Interestingly, it appears that these medications might actually lower the risk of developing the disease.
“Alzheimer’s involves complex changes in the brain, making it challenging to study and treat,” shares computational biologist Marina Sirota from UCSF. “However, our innovative computational tools gave us the potential to directly address this complexity.”
“We’re excited that our computational findings pointed us towards a possible combination therapy for Alzheimer’s using currently FDA-approved medications.”
After identifying letrozole and irinotecan as promising options, the team experimented with them in mouse models representing Alzheimer’s. Remarkably, when administered together, these drugs seemed to reverse several brain changes associated with the disease.
The harmful buildups of tau protein linked to Alzheimer’s were significantly decreased, and the mice showed notable improvements in learning and memory capabilities – areas that are often impaired in Alzheimer’s.
Using the drugs in combination allowed the researchers to target different types of brain cells affected by the illness. Letrozole appeared to focus on neurons, while irinotecan seemed to benefit glial cells.
“Alzheimer’s is probably due to a multitude of changes in various genes and proteins that together compromise brain health,” remarks neuroscientist Yadong Huang from UCSF and Gladstone. “This complexity poses a significant challenge for drug development, which typically aims to create a single drug for one specific gene or protein linked to a disease.”
While this initial discovery is certainly promising, much work lies ahead. It’s important to note that these drugs have only been tested directly in mice so far, and they also come with their own side effects. Any contemplation of repurposing them for Alzheimer’s must account for these factors.
Moving forward, clinical trials involving individuals with Alzheimer’s disease should be the next step. The researchers believe that this approach could foster more personalized and effective treatments based on how gene expression varies in different individuals.
It’s estimated that over 55 million individuals currently live with Alzheimer’s, and as the world’s population ages, that number is expected to more than double in the next 25 years. Finding avenues for prevention and potential reversal of symptoms could have a monumental impact on global health.
“If completely independent data sources, such as single-cell gene expression data alongside clinical records, lead us to the same pathways and medications, and can resolve Alzheimer’s in genetic models, we might be onto something,” Sirota adds.
“We’re hopeful that we can quickly translate this into a real solution for millions battling Alzheimer’s.”
The findings from this research have been published in Cell.
