Existing Medications May Hold Key to Reversing Alzheimer’s Progression
In the ongoing battle against Alzheimer’s disease, researchers are exploring existing medications that might offer new hope, and a recent study has identified two promising candidates currently used in cancer treatment.
Already Approved for Human Use
These drugs – letrozole (typically used for breast cancer treatment) and irinotecan (commonly prescribed for colon and lung cancer) – have already received regulatory approval in the United States, potentially allowing clinical trials for Alzheimer’s to begin more quickly.
Innovative Research Approach
Scientists from the University of California, San Francisco (UCSF) and Gladstone Institutes began by examining how Alzheimer’s disease alters gene expression patterns in the brain.
They then utilized a medical database called the Connectivity Map to identify drugs that could reverse these genetic changes. The researchers cross-referenced data from cancer patients who had taken these medications and their subsequent likelihood of developing Alzheimer’s disease. Interestingly, the drugs appeared to reduce their risk.
Scientific Perspective
“Alzheimer’s disease involves complex changes to the brain, which has made it challenging to study and treat,” explains computational biologist Marina Siroto from UCSF. “However, our computational tools opened up the possibility of tackling this complexity directly.”
“We’re excited that our computational approach led us to a potential combination therapy for Alzheimer’s based on existing FDA-approved medications.”
Laboratory Success
The researchers tested letrozole and irinotecan in mouse models of Alzheimer’s disease. When used together, the drugs successfully reversed some of the brain changes associated with the condition.
The harmful tau protein accumulations that characterize Alzheimer’s-affected brains were significantly reduced, and the mice demonstrated improved performance in learning and memory tasks – cognitive abilities typically impaired by the disease.
Targeting Different Brain Cells
By combining the two medications, researchers were able to target various types of brain cells affected by Alzheimer’s. Letrozole appeared to combat the disease’s effects in neurons, while irinotecan worked effectively in glial cells.
Understanding the Complexity
“Alzheimer’s is likely the result of numerous alterations in many genes and proteins that, together, disrupt brain health,” notes neuroscientist Yadong Huang from UCSF and Gladstone. “This makes drug development very challenging – traditional approaches typically produce one drug for a single gene or protein that drives disease.”
Next Steps and Considerations
While these results are encouraging, additional research is necessary. The drugs have only been directly tested in mice so far, and these medications do come with potential side effects. Careful reconsideration will be needed if the drugs are to be repurposed for a different condition than their original approval.
Clinical trials involving human Alzheimer’s patients represent one of the next crucial steps. According to the researchers, this approach could lead to more personalized and effective treatments based on individual gene expression patterns.
Global Health Impact
It’s estimated that more than 55 million people currently live with Alzheimer’s disease, and as the world’s population ages, this number is expected to more than double within the next 25 years. Finding ways to prevent the disease and potentially reverse its symptoms would have a tremendous impact on global health.
Researcher Optimism
“If completely independent data sources, such as single-cell expression data and clinical records, guide us to the same pathways and the same drugs, and then resolve Alzheimer’s in a genetic model, then maybe we’re on to something,” says Sirota.
“We’re hopeful this can be swiftly translated into a real solution for millions of patients with Alzheimer’s.”
Research Publication
The study has been published in Cell.
