With few treatments available to stop or reverse Alzheimer’s disease, scientists are turning to cancer drugs as a potential means of cognitive decline.
Alzheimer’s cases are increasing due to the aging population in the US and around the world, but there is no cure for the disease. Attempts to develop new treatments that slow the progression of the disease rather than alleviating symptoms have frequently failed.
Only two drugs, antibody therapy Leqembi and Kisunla, are currently approved by the Food and Drug Administration to slow the progression of early Alzheimer’s disease, and scientists say their benefits are limited.
Some pharmaceutical companies have suspended or abandoned their Alzheimer’s drug development program due to failing their trials. Others are trying to combat Alzheimer’s disease using existing medications, including popular weight loss pills.
With that in mind, University of California researcher San Francisco conducted a wide range of searches for drugs that can be reused to treat the condition. In theory, it reduces the time it takes for patients to make the drug accessible. They scrutinized a database of over 1,300 drugs in a variety of classes, including antipsychotics, antibiotics, antifungals, and chemotherapeutics. We then looked at how those drugs affected gene expression.
Their new study, published in the journal Cell on Monday, identified two cancer drugs as the best candidates to reduce patients’ risk of Alzheimer’s disease. When combined, the drug appeared to slow or reverse symptoms of Alzheimer’s disease in mice. One of the drugs is usually used to treat breast cancer, while the other is effective against colon and lung cancer.
Alzheimer’s disease is associated with significant changes in the way genes are expressed in the brain, leading to increased production of certain proteins and reduced production of others. These imbalances can disrupt brain function and contribute to symptoms such as amnesia.
Less than 90 drugs in the researcher’s database reversed the expression of signature Alzheimer’s disease-related genes in human brain cells. And five drugs in particular appeared to reduce the risk of Alzheimer’s disease in real patients, based on electronic medical records. The authors ultimately selected two FDA-approved drugs to treat cancer for testing in mice.
“We didn’t expect cancer drugs to come up,” said Marina Sirota, interim director of the UCSF Bakar Computational Health Sciences Institute, as the most promising thing.
The authors stated that letrozole breast cancer drug appears to alter gene expression in neurons. And the colon cancer drug irinotecan appears to alter gene expression in glial cells that support the nervous system. Alzheimer’s disease destroys nerve cells, proliferates glial cells, and causes inflammation of the brain.
A 2020 study found that breast cancer patients receiving letrozole were less likely to develop Alzheimer’s disease than patients who were not given the drug. A 2021 survey found that colorectal cancer survivors treated with irinotecan also had a lower risk of Alzheimer’s disease.
After testing the drugs in mice, the study authors found that the two-drug combo reversed brain degeneration and improved memory in mice that developed the characteristics of Alzheimer’s disease during the aging of Alzheimer’s disease.
As results in mice are often not translated into humans, researchers hope to test the drug in clinical trials with Alzheimer’s disease patients.
“Developing a new drug costs millions, or even billions, on average. It takes over 10 years. This recycled drug usually takes two or three years. You can go to clinical trials and the costs are much lower.
“We are not yet producing or producing highly effective drugs that can dramatically slow down cognitive decline,” he added.
Part of the difficulty in developing Alzheimer’s drugs is the complexity of the disease. The exact cause is largely unknown.
For now, the authors said it is unclear exactly why cancer drugs appear to be working against Alzheimer’s disease. One theory is that breast cancer drugs block the production of estrogen, a hormone that regulates the expression of many genes. Colon cancer drugs can prevent brain inflammation by preventing glial cell growth, but Huang says there are other possibilities.
Dr. Melanie McReynolds, an assistant professor of biochemistry at Penn State University who was not involved in the study, provided another theory.
Her research suggests that different types of cancer drugs can help treat Alzheimer’s disease by regulating glucose metabolism, the process by which cells produce energy. McReynolds said this process is necessary for various brain cells to communicate with each other.
“Aging, stressful, illness, that line of communication is destroyed,” she said.
McReynolds said the drug combos tested in a new study could reverse metabolism decline.
However, it is important to assess how Alzheimer’s patients with endure cancer drug combinations. Letrozole can cause hot flashes, and irinotecan can cause severe diarrhea. Both drugs can lead to nausea and vomiting.
“These drugs have major side effects, so you need to always balance it and understand whether these types of side effects are suitable for people with Alzheimer’s,” Shirota said. “It’s not like it’s a slam dunk.”
