Cancer Drugs Show Promise Against Alzheimer’s

Repurposed Medications May Reverse Brain Damage

A groundbreaking study is exploring the potential of existing cancer drugs to combat Alzheimer’s disease. Researchers have identified two medications, already approved for cancer treatment, that may help reverse key brain changes associated with the debilitating neurological condition.

Targeting Alzheimer’s Through Gene Expression

Scientists at the University of California, San Francisco (UCSF) and Gladstone Institutes began by examining how Alzheimer’s disease alters gene expression within the brain. They then utilized the Connectivity Map, a comprehensive medical database, to identify drugs capable of counteracting these specific genetic alterations.

This computational approach led to the selection of letrozole, a drug commonly used for breast cancer, and irinotecan, prescribed for colon and lung cancers. The researchers found that patients treated with these drugs for cancer appeared to have a reduced risk of developing Alzheimer’s.

“Alzheimer’s disease comes with complex changes to the brain, which has made it tough to study and treat, but our computational tools opened up the possibility of tackling the complexity directly,” says computational biologist Marina Sirota, from UCSF.

“We’re excited that our computational approach led us to a potential combination therapy for Alzheimer’s based on existing FDA-approved medications.”

Success in Animal Models

In tests conducted on mouse models of Alzheimer’s, the combination of letrozole and irinotecan demonstrated a significant ability to reverse some of the disease’s pathological hallmarks. Notably, the drugs were effective in reducing the accumulation of tau protein, a key marker of Alzheimer’s in the brain.

Furthermore, the treated mice exhibited improved performance in learning and memory tasks, cognitive functions frequently impaired by Alzheimer’s. The study suggests letrozole targets neurons, while irinotecan acts on glia, suggesting a multifaceted approach to tackling the disease.

“Alzheimer’s is likely the result of numerous alterations in many genes and proteins that, together, disrupt brain health,” says neuroscientist Yadong Huang, from UCSF and Gladstone.

“This makes it very challenging for drug development – which traditionally produces one drug for a single gene or protein that drives disease.”

Next Steps and Global Impact

While these findings are promising, researchers emphasize that the drugs have only been tested in mice thus far. Potential side effects of these medications must also be carefully re-evaluated for their suitability in treating Alzheimer’s. The next critical step involves initiating clinical trials in human patients.

This innovative strategy could pave the way for more personalized and effective treatments, tailored to the specific genetic profile of each patient. With over 55 million people worldwide currently living with Alzheimer’s, and this number projected to more than double in the next 25 years, finding new therapeutic avenues is of paramount global importance. The research has been published in the journal Cell.