Two FDA-approved cancer medications may hold the key to slowing — or potentially reversing — Alzheimer’s disease, according to groundbreaking research from the University of California, San Francisco (UCSF).
In a study published July 21 in the journal Cell, UCSF researchers used computational methods to identify how Alzheimer’s disease alters gene expression in brain cells. They then searched for existing drugs that might reverse these molecular changes — and zeroed in on two anticancer agents: letrozole, commonly used for breast cancer, and irinotecan, approved for colon and lung cancers.
Data-Driven Drug Discovery Offers New Hope
By analyzing millions of electronic medical records from patients aged 65 and older, the researchers found that individuals prescribed these drugs had a lower likelihood of developing Alzheimer’s. When tested in mouse models, the combination of letrozole and irinotecan reversed Alzheimer’s-related gene expression changes.
Notably, the treatment also reduced accumulations of tau protein — one of the disease’s hallmarks — and improved cognitive performance in learning and memory tests.
“Alzheimer’s comes with complex changes to the brain, making it hard to study and treat,” said Dr. Marina Sirota, co-senior study author and interim director of the UCSF Bakar Computational Health Sciences Institute. “Our computational tools helped us confront that complexity, leading to a promising potential combination therapy using already FDA-approved medications.”
Limitations and Next Steps
Despite the promising findings, the authors acknowledged key limitations. The computational model was initially developed using cancer cell data, not brain cells. Additionally, the preclinical tests were performed in mice, and may not fully reflect human biology.
The team also observed gender-related differences in the animal studies. Male mice showed a stronger therapeutic response than females — a difference researchers suspect could be related to letrozole’s hormone-modulating effects. However, due to the small number of male letrozole users in the data, the results are inconclusive.
Electronic medical records, while vast, may lack critical detail and were not originally collected for targeted research, further limiting the certainty of the findings.
Urgent Need for New Treatments
More than 7 million Americans are currently living with Alzheimer’s, and that figure is projected to surge to nearly 13 million by 2050, according to the Alzheimer’s Association.
Currently, the only disease-modifying Alzheimer’s treatments approved by the FDA are lecanemab (Leqembi) and donanemab (Kisunla). These monoclonal antibodies work by reducing amyloid plaque buildup in the brain but are only effective in the disease’s early stages and carry the risk of serious side effects.
“Alzheimer’s is likely driven by numerous disruptions in a complex network of genes and proteins,” said Dr. Yadong Huang, co-senior author and UCSF professor of neurology and pathology. “Traditional drug development — which targets one protein or pathway at a time — struggles to meet this challenge.”
Toward Human Trials
The UCSF team now hopes to move their findings from mice to humans. Plans are underway to launch clinical trials testing the efficacy of the drug combination in patients with Alzheimer’s.
“If entirely separate data sources — from single-cell gene expression to large-scale medical records — point to the same drugs and pathways, and we see results in an animal model, we may be onto something truly significant,” Sirota added.
The study was supported in part by the National Institutes of Health (NIH) and the National Science Foundation (NSF).
READ MORE
2 FDA-Approved Oncology Medications Reprogram Alzheimer’s Genes
Could HIV Medications Help Prevent Alzheimer’s Disease?
Should You Get Tested For Alzheimer’s Even Without Symptoms?
