New Hope for Alzheimer’s Treatment with Existing Cancer Drugs

Researchers aiming to address Alzheimer’s disease may have identified two promising drug candidates.

These are already approved medications used in the treatment of cancer, which is quite exciting. This means potential clinical trials for Alzheimer’s patients could kick off sooner. The drugs, letrozole and irinotecan, are typically used for treating breast cancer and colon or lung cancer, respectively.

The team of researchers from the U.S. began their investigation by looking at how Alzheimer’s modifies gene expression in the brain. They then utilized a medical database called the Connectivity Map to find drugs that might reverse these gene expression changes. They also cross-referenced this with data from patients who had been treated with these drugs for cancer, discovering a reduced risk of developing Alzheimer’s.

“Alzheimer’s disease involves intricate changes in the brain, making it difficult to study and treat, but our computational tools have opened up new possibilities,” explains computational biologist Marina Sirota from UC San Francisco. “We’re excited that our approach led us to a combination therapy for Alzheimer’s based on existing FDA-approved medications.”

After identifying letrozole and irinotecan as strong candidates, the researchers tested them on mouse models of Alzheimer’s, and found that using the two drugs together could reverse some of the brain changes caused by the disease.

Significantly, the drugs decreased harmful clumps of tau protein in the mice’s brains, and the animals showed improvements in learning and memory—two critical areas often affected by Alzheimer’s.

By combining these drugs, the researchers targeted various types of brain cells influenced by Alzheimer’s. Letrozole seemed effective in neurons, while irinotecan appeared to work well in glial cells.

“Alzheimer’s likely stems from many alterations in numerous genes and proteins together disrupting brain health,” says neuroscientist Yadong Huang from UC San Francisco and Gladstone Institutes. “This complexity presents challenges in drug development, which usually benefits from targeting a single gene or protein.”

This initial finding is promising, yet there’s more to explore: the drugs have only been tested in mice so far, and they come with potential side effects. These factors will need careful consideration if the drugs are repurposed for Alzheimer’s.

Future steps would ideally include conducting clinical trials with human subjects suffering from Alzheimer’s. The researchers believe this could pave the way for more personalized and effective treatments, tailored to how gene expression varies in each case.

Currently, over 55 million people are living with Alzheimer’s, a figure that may more than double in the next 25 years as the population ages. Identifying ways to prevent or even reverse the symptoms would significantly impact global health.

“If independent data sources like single-cell expression records and clinical data lead us to the same drugs and pathways, and it resolves Alzheimer’s in a genetic model, then perhaps we’re making real progress,” reflects Sirota. “We’re hopeful that this can be quickly turned into an actual solution for millions of individuals with Alzheimer’s.”

The findings are published in Cell.