In a groundbreaking study, researchers at the University of California, San Francisco have identified two existing cancer drugs that could potentially be repurposed to treat Alzheimer’s disease, which is increasingly affecting an aging population both in the United States and worldwide.
As the number of Alzheimer’s cases continues to rise, the search for effective treatments has become more urgent, especially since there is currently no cure for the disease.
With only two FDA-approved drugs—antibody therapies Leqembi and Kisunla—available to slow progression in early Alzheimer’s cases, scientists are exploring new avenues to address this debilitating condition.
The harsh reality has led several pharmaceutical companies to abandon their Alzheimer’s drug development programs following unsuccessful trials, while others pursue the repurposing of existing medications, including weight loss drugs.
This recent research aimed to tap into a database of over 1,300 drugs from various classes—ranging from antipsychotics to chemotherapy agents—to find existing treatments that could alleviate Alzheimer’s symptoms.
The findings were published in the journal Cell, revealing two cancer drugs as particularly effective in lowering Alzheimer’s risk when tested in combination on mice.
One of these drugs is letrozole, typically used in breast cancer treatment, while the other, irinotecan, is effective against colon and lung cancers.
Alzheimer’s disease disrupts normal brain function due to significant changes in gene expression, contributing to symptoms like memory loss.
The research team discovered that fewer than 90 of the drugs in their database reversed Alzheimer’s-related gene expression in human brain cells.
Among these, five drugs were identified as lowering Alzheimer’s risk based on electronic medical records, leading to the selection of letrozole and irinotecan for animal testing.
Marina Sirota, a co-author of the study and interim director of the UCSF Bakar Computational Health Sciences Institute, expressed surprise at finding cancer drugs to be the most promising candidates.
The study found that letrozole appeared to influence gene expression in nerve cells, whereas irinotecan affected glial cells, which support the nervous system.
Since Alzheimer’s can destroy nerve cells and induce inflammation through glial cell proliferation, this dual mechanism presents an intriguing therapeutic angle.
Notably, previous studies have linked letrozole use among breast cancer patients with a lower incidence of developing Alzheimer’s.
Similarly, colorectal cancer survivors treated with irinotecan exhibited a reduced risk for Alzheimer’s, further supporting the rationale for this research.
After administering the drug combination to mice showing Alzheimer’s hallmarks as they aged, researchers observed a reversal of brain degeneration and memory improvement.
This research holds considerable promise, as developing new drugs can be an extensive and costly process, often taking years and significant financial investment.
Dr. Yadong Huang, another co-author and professor of neurology at UCSF, highlighted that repurposing existing medications could expedite clinical trials and lower costs considerably.
Despite the encouraging results, challenges in drug development for Alzheimer’s persist due to the complexity and mystery surrounding its causes.
Research reveals that one possible mechanism for the effectiveness of these cancer drugs might lie in their ability to block estrogen production—one of the theories supporting the role of letrozole.
In addition, irinotecan may prevent glial cell proliferation and inflammation, although researchers emphasize that other mechanisms could also be at play.
Opinions from experts outside the study, such as Dr. Melanie McReynolds from Pennsylvania State University, suggest that understanding metabolic processes could also play a crucial role in addressing Alzheimer’s.
McReynolds noted that disruptions in glucose metabolism hinder communication between brain cells, and cancer drugs that regulate this process may aid in treating Alzheimer’s.
While the potential for these cancer drugs is exciting, researchers recognize the importance of examining how Alzheimer’s patients would tolerate the side effects.
Letrozole can lead to hot flashes, and irinotecan is associated with severe diarrhea, nausea, and vomiting, raising the question of whether the benefits would outweigh the side effects for patients with Alzheimer’s.
Sirota cautioned against assuming the benefits would be clear-cut, emphasizing the need for cautious evaluation.
As the research progresses toward clinical trials, the scientific community remains hopeful that combining these repurposed cancer drugs could pave the way for new treatment options.
While the pathway is fraught with uncertainty, these findings rekindle optimism in the ongoing battle against Alzheimer’s, a disease that tragically robs individuals of their cognitive abilities and independence.
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