ALZHEIMER'S DISEASE TREATMENT: CANCER DRUGS SHOWN EFFECTIVE





Researchers at UC San Francisco and Gladstone Institutes may have found a way to reverse Alzheimer’s—using two drugs that were initially developed to fight cancer. By analyzing gene expression data, the team found that certain FDA-approved cancer drugs can counteract the changes Alzheimer’s disease makes in the brain.

Their approach started with a big question: Which genes go haywire in Alzheimer’s, and are there any existing drugs that flip those gene changes back to normal? The researchers compared the altered gene patterns in brain cells from Alzheimer’s patients to the effects of more than 1,300 medications. Their goal was to find drugs that could reverse the damage, especially in neurons and glia, the two cell types hit hardest by the disease.

They didn’t stop at the lab. The team also combed through millions of anonymous medical records and noticed that people who had been treated with certain cancer drugs seemed less likely to develop Alzheimer’s later on.

When they tested the top two drug candidates—both cancer medications—in mice bred to develop Alzheimer’s, the results were dramatic. The drugs not only slowed brain degeneration but also restored the animals’ memory. “Alzheimer’s is tough to crack because it messes with so many genes at once,” said Dr. Marina Sirota, co-senior author of the study. “But by using computational tools, we were able to see the bigger picture—and find a combination of existing drugs that could help.”

The breakthrough, published in Cell on July 21, was supported by the National Institutes of Health and the National Science Foundation.

A New Way to Treat Alzheimer’s?

Nearly 7 million Americans live with Alzheimer’s, a disease that steadily erodes memory and thinking skills. Until now, only two drugs have been approved to treat it—and neither can significantly slow the decline.

“This disease isn’t caused by just one faulty gene or protein. It’s a whole network of changes,” said Dr. Yadong Huang, the study’s other co-senior author. To tackle that complexity, the team used publicly available single-cell gene expression data from Alzheimer’s patients and compared it to a massive database that tracks how thousands of drugs impact genes in human cells.

Out of 1,300 drugs, 86 could reverse some of the harmful gene changes. Only 10 had already been approved for use in people. The researchers then turned to the UC Health Data Warehouse, a database of health records from over 1.4 million older adults. By looking for connections between these drugs and Alzheimer’s risk, they narrowed the list to the most promising candidates.

The final lab tests focused on two cancer drugs: letrozole, usually used for breast cancer, and irinotecan, used for colon and lung cancers. In mice with aggressive Alzheimer’s mutations, these drugs reversed many disease-related changes in brain cells, reduced toxic protein clumps, and brought back lost memory.

“We were thrilled to see that our data-driven approach worked in an animal model,” Dr. Huang said—the next step: clinical trials in human patients.

“If totally independent sources—cell data and clinical records—lead us to the same drugs, and those drugs work in animals, we may be onto something big,” said Dr. Sirota. “We hope to move this therapy into patient testing as soon as possible.”

The research team included scientists from UCSF and Gladstone Institutes, with support from the National Institute on Aging, the National Science Foundation, and the Dolby Family Fund.

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