Cancer Drugs Show Promise in Reversing Alzheimer’s Symptoms, New Research Reveals
A groundbreaking study published on July 21 suggests that existing cancer drugs may hold the key to reversing the debilitating effects of Alzheimer’s disease, offering a potential new avenue for treatment and hope for the 7 million Americans currently living with the condition.
Researchers at UC San Francisco and the Gladstone Institutes have identified a combination therapy that, in preclinical trials, not only slowed the progression of Alzheimer’s but demonstrably restored cognitive function in a mouse model. This innovative approach leverages the power of big data and computational tools to repurpose already-approved medications, potentially accelerating the path to effective treatments.
Unlocking Alzheimer’s Complexity with Computational Power
For decades, Alzheimer’s disease has remained a formidable challenge for medical science. The disease, characterized by a relentless decline in cognition, learning, and memory, has yielded only limited therapeutic options. “Alzheimer’s is likely the result of numerous alterations in many genes and proteins that, together, disrupt brain health,” explained a senior investigator involved in the study. “This makes it very challenging for drug development – which traditionally produces one drug for a single gene or protein that drives disease.”
The research team tackled this complexity by first analyzing how Alzheimer’s alters gene expression in individual cells within the human brain. They then searched for existing drugs approved by the Food and Drug Administration (FDA) that could counteract these changes. The focus was on reversing alterations in both neurons and glia, critical brain cells damaged by the disease.
From Millions of Records to a Promising Drug Combination
The team’s innovative approach involved analyzing millions of electronic medical records from the UC Health Data Warehouse, encompassing data on over 1.4 million individuals over the age of 65. This analysis revealed that patients who had previously taken certain drugs for other conditions were less likely to develop Alzheimer’s.
“Thanks to all these existing data sources, we went from 1,300 drugs, to 86, to 10, to just 5,” said a lead author of the study. “In particular, the rich data collected by all the UC health centers pointed us straight to the most promising drugs. It’s kind of like a mock clinical trial.”
Ultimately, the researchers zeroed in on two cancer drugs – letrozole and irinotecan – as the most promising candidates. Letrozole is commonly used to treat breast cancer, while irinotecan is used for colon and lung cancer.
Restoring Memory in a Mouse Model
In laboratory testing, the combination of letrozole and irinotecan demonstrated remarkable results in a mouse model of aggressive Alzheimer’s disease. The drugs reversed the disease’s impact on gene expression in both neurons and glia, reduced the formation of toxic protein clumps, and significantly lessened brain degeneration. Most importantly, the treatment restored the mice’s ability to remember.
“It’s so exciting to see the validation of the computational data in a widely used Alzheimer’s mouse model,” said a senior researcher. The team anticipates moving quickly toward a clinical trial to test the combination therapy directly in Alzheimer’s patients.
“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 onto something,” stated a co-senior author of the paper. “We’re hopeful this can be swiftly translated into a real solution for millions of patients with Alzheimer’s.”
The research was funded by the National Institutes of Health, the National Science Foundation, and the Dolby Family Fund.
