A pair of FDA-approved cancer drugs may help reverse the biological changes that drive Alzheimer’s disease, according to a new study from researchers at UC San Francisco and the Gladstone Institute. The findings could mark a significant step forward in treating a condition that affects more than 7 million people in the U.S.
Despite decades of research, only two drugs have been FDA-approved to treat Alzheimer’s, and neither meaningfully slows the disease’s relentless cognitive decline. That’s why this new study took a novel approach: using data science to search for untapped potential in medicines already on the market.
“We started with 1,300 drugs — a lot were cancer drugs, but we didn’t have a hypothesis like that. This was entirely data-driven. And it was a bit of a surprise,” said Marina Sirota, a professor at UCSF and interim director of the Baker Computational Health Sciences Institute.
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Dr. Yaqiao Li, a former UCSF graduate student in Sirota’s lab and now a postdoctoral scholar at the Gladstone Institute, led the research in hopes of identifying a solution for patients to restore their brain function impacted by the disease. Their team tapped into the Connectivity Map, a large-scale drug database, to analyze how existing compounds impact the brain on a molecular level.
It turned out that two cancer drugs stood out: letrozole, which is used to treat breast cancer, and irinotecan, which is typically used by colon and lung cancer patients. When the researchers tested a combination of the two drugs in a mouse model of Alzheimer’s, it slowed down brain generation and even restored their ability to remember.
“These are FDA-approved drugs. And we have human evidence that cancer patients who have taken these drugs have a lower risk of developing Alzheimer’s,” said Dr. Li. “This gives me a lot more confidence that this could be very promising.”
Developing a brand-new Alzheimer’s drug from scratch can cost millions and take more than a decade. But because the drugs in this study are already FDA-approved — just for a different condition — the path to clinical trials and eventual use for Alzheimer’s could be much shorter. The researchers tell Scripps News they are currently fundraising to begin a human clinical trial, where they note significant side effects will need to be considered.
The FDA recently approved donanemab, an Alzheimer’s drug from Eli Lilly, but many pharmaceutical companies have abandoned similar projects after unsuccessful trials. That makes the possibility of repurposing existing drugs, with known safety profiles, especially appealing.
The findings from this study indicate potential success in repurposing for other complex diseases, like endometriosis, which Sirota says they are currently working on in their lab.
“I just want to encourage future researchers,” Dr. Li said, “This could be a very interesting, promising new way of doing drug discovery.”
