Cancer drug bexarotene effective in mouse model of Alzheimer’s

A drug that is approved for the treatment of a type of skin cancer since 1999 has shown to reverse Alzheimer's symptoms in lab mice.

Case Western Reserve University School of Medicine neuroscientist Gary Landreth and colleagues reported Thursday that the drug - bexarotene quickly cleared away beta-amyloid plaque, believed to cause the cognitive deficits of Alzheimer's disease, from the brains of genetically engineered mice.

They found that mice who received bexarotene treatment regained memory and cognitive function, including improvements in their sense of smell. The Alzheimer’s-afflicted mice were able to resume normal behaviors, such as shredding paper for nest building, three days after treatment. Bexarotene worked by helping to increase levels of a protein called Apolipoprotein E (ApoE), which helps remove beta-amyloids.  Its effects took hold quickly, with half of plaques removed within 72 hours, the authors reported.

Paige Cramer, a Ph.D. candidate at Case Western Reserve, said in a statement that the research had produced “an unprecedented finding,” noting that the previous best treatment for Alzheimer's in mice took several months to reduce plaque. As a consequence of aging, the ability to clear plaque from the brain goes down, and we are able to enhance ApoE,” Cramer said. “The benefit of this drug is we are just facilitating or enhancing Mother Nature.” The study appeared online in the journal Science.

Scientists warn that it would take six years or longer before bexarotene might be used to treat people with the degenerative brain disease. “Ultimately, you have to test this in humans,” said Dr. Lon S. Schneider, an Alzheimer's researcher at USC's Keck School of Medicine in Los Angeles.  Schneider said that efficacy trials would involve enrolling 1,000 patients for 18 months of treatment - a process that would take more than three years. Further tests would take an additional couple of years. And then the treatment would have to work, he added. “It's very uncommon, so far, that treatments for mice translate for humans,” he said. “People should not get immediately excited, or try to buy this drug from Canada,” he warned.

“It’s still an animal study, and it still needs to be moved into humans. But it is exciting and is a novel approach,” said Maria Carrillo, senior director of medical and scientific relations for the Alzheimer’s Association.

Dr. George Bartzokis of the Brain Research Center at UCLA agreed that the track record for curing Alzheimer's in people with “mouse cures” was poor. He said, though, that this kind of discovery is “exciting because it has the potential to give another clue in the puzzle of Alzheimer's disease.”

Bartzokis said that he would like to have learned the effects of bexarotene on myelin (the fatty insulation that protects neurons) in the mice. “The medication these investigators used acted by increasing several enzymes...involved in building up and repairing myelin,” he said.  If the treatment turns out to help repair myelin in humans, it could have applications to several important diseases in addition to Alzheimer's disease.

Dr. William Klunk, co-director of the Alzheimer’s Disease Research Center at the University of Pittsburgh, said the current study on bexarotene opens an exciting new avenue for the potential successful treatment of the disease. But he remains cautiously optimistic. “We in this field have seen enough success in mouse studies not pan out in human studies to know this is just the beginning and there’s a long way to go,” Klunk said.

Because bexarotene is known to be safe for treating skin cancer, “it might be worth trying in Alzheimer's patients as well,” said Rada Koldamova, a neuroscientist who works on Alzheimer's at the University of Pittsburgh and wasn't involved in the study.

In the U.S., bexarotene is sold under the name Targretin, which is owned and marketed by Japan's Eisai Co. Patents on the drug will start to expire this year, one reason drug companies may be reluctant to jump on bexarotene as a possible Alzheimer's treatment. There are roughly 5.4 million Americans living with Alzheimer’s.

Dr. Ananya Mandal

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Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

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