Skin Cancer Drug Treats Late-Stage Dementia in Mice
A common skin cancer drug could treat Alzheimer's disease, according to a new study.
Scientists found that bexarotene, an anti-cancer drug approved to treat cutaneous T-cell lymphoma in patients whose disease could not be treated successfully with other medications.
Previous findings showed conflicting results as bexarotene reduced levels of amyloid-beta in experimental mice with late-stage Alzheimer's but increased levels in rodents dealing with early stages of the neurodegenerative disease.
In 2012, scientists engineered a mouse that is now thought of as the best animal model of Alzheimer's disease. The genetically engineered mouse carries a human gene that increases the risk of Alzheimer's disease by 15 times. Researchers explained that humans generally carry a gene for a protein in cells called apolipoprotein E, which helps clear amyloid-beta from the brain by binding to it and destroying it. However, the genetically engineered mice carry the variant called APOE4, or APOE3, which is neutral for Alzheimer's disease risk.
"APOE4 is the greatest genetic risk factor for Alzheimer's disease," researcher Mary Jo LaDu, a professor of the University of Illinois at Chicago College of Medicine, said in a news release. "Our previous work showed that compared to APOE3, the apolipoprotein produced by the APOE4 gene does not bind well to amyloid-beta and so does not clear the neurotoxin from the brain."
In the latest study, researchers administered bexarotene to mice carrying APOE4 or APOE3 for seven days during the early, intermediate, or late stages of Alzheimer's disease. Researchers then assessed the levels of soluble amyloid-beta in the brains of the laboratory mice.
The findings revealed a 40 percent decrease in soluble amyloid-beta and an increase in the binding of apolipoprotein to amyloid-beta in mice experiencing the later stages of Alzheimer's disease. However, amyloid-beta actually increased in APOE4 or APOE3 mice with earlier-stage Alzheimer's disease. Furthermore, the study revealed no beneficial affect for APOE4 mice administered bexarotene for one month starting when they had early-stage Alzheimer's disease.
Researchers said the findings suggest that short-term treatment with bexarotene in the later stages of Alzheimer's is more beneficial for people carrying the APOE4 gene. However, more research is needed to reveal the length and timing of treatment.
"Bexarotene also is extremely toxic to the liver," co-researcher Leon Tai, research assistant professor in anatomy and cell biology, said in a statement. "For prevention, where a drug is given before the symptoms of Alzheimer's disease appear, and likely over longer periods of time, bexarotene is not likely a viable therapeutic because of this known toxicity unless dosing is carefully controlled and patients are closely monitored."
The findings were published in The Journal of Biological Chemistry.