ALZHEIMER'S DISEASE TREATMENT UPDATE

Scientists at UC San Francisco and the Gladstone Institutes might be on the verge of something extraordinary: reversing Alzheimer’s disease with drugs originally designed to fight cancer. In a field where progress too often feels painfully slow, their approach stands out for its creativity and its promise.

Here’s how it happened. Instead of starting with a single protein—the way most Alzheimer’s drug efforts do—the team looked at the mess Alzheimer’s makes of the brain’s genetic code. Using powerful computational tools, they compared gene activity from Alzheimer’s patients’ brain cells with the effects of over 1,300 existing drugs. The idea: find medications that could undo the gene-level chaos unleashed by the disease, especially in neurons and glia—the brain’s most vulnerable cells.

It wasn’t just a numbers game. The researchers also dug into millions of anonymous medical records, searching for real-world clues. They noticed something odd: patients who’d taken certain cancer drugs seemed less likely to develop Alzheimer’s later in life.

That’s when things got really interesting. When the team tested their top two candidates—letrozole, a breast cancer drug, and irinotecan, used for colon and lung cancers—on mice genetically engineered to develop Alzheimer’s, the results were dramatic. The drugs didn’t just slow the disease; they reversed brain degeneration and brought lost memories back.

“Alzheimer’s is incredibly complex,” said Dr. Marina Sirota, a co-senior author of the study. “It scrambles hundreds of genes at once. But with computational biology, we can finally see the bigger picture and find solutions hiding in plain sight.”

This work, published in Cell , represents a leap forward in a field hungry for new ideas. Nearly 7 million Americans live with Alzheimer’s, and despite recent excitement over new antibody treatments like lecanemab and donanemab, none have managed to halt the disease’s relentless march. Most new drugs target amyloid plaques or tau tangles—just two pieces of a much larger puzzle.

“Alzheimer’s isn’t caused by a single broken part,” said Dr. Yadong Huang, the study’s other co-senior author. “It’s a whole tangled network. That’s why we turned to big data and gene expression: to find drugs that can reset the system, not just patch one leak.”

After sifting through 1,300 drugs, they found 86 that could reverse some of the gene changes seen in Alzheimer’s. Only 10 were already FDA-approved. Combining this with medical record analysis from over 1.4 million older adults, they narrowed it down to letrozole and irinotecan.

When tested in mice with aggressive Alzheimer’s mutations, both drugs reduced toxic protein build-up, reversed cell damage, and restored lost memory. “Seeing this kind of effect in animals is rare,” Dr. Huang said. “Our next step is clinical trials in people. If these results hold up, we might finally have tools to fight back against this devastating disease.”

Dr. Sirota is hopeful but cautious. “The fact that both our lab experiments and real-world health data point to the same drugs is a powerful signal. We’re eager to move forward and see if this approach can help patients.”

The study, supported by the National Institute on Aging, the National Science Foundation, and the Dolby Family Fund, marks a turning point in how scientists are thinking about—and fighting—Alzheimer’s. With new research from around the world showing that gene networks and immune system changes may be just as important as amyloid and tau, the field is finally widening its scope. For patients and families, that can’t come soon enough.