Pitt researchers verify cancer drug improves Alzheimer's symptoms in mice

Chris Togneri
| Thursday, May 23, 2013, 2:09 p.m.

University of Pittsburgh researchers have confirmed that a federally approved cancer drug reverses cognitive disabilities in mice with symptoms of Alzheimer's disease.

Rada Koldamova, associate professor at the Pitt Graduate School of Public Health, called the results encouraging but cautioned that the findings do not mean a cure is imminent.

“We should not give false promises for something that could take years to be approved,” Koldamova said. “But from an experimental point of view, it's very encouraging.”

The researchers' findings were published on Thursday in the journal Science. The work confirms the results of a study published last year by researchers at Case Western Reserve University in Cleveland.

That team found that the drug bexarotene, approved by the Food and Drug Administration in 1999 for use in cutaneous T cell lymphoma, improved memory and brain functions in mice genetically engineered to show Alzheimer's symptoms.

The disease causes a slow decline in memory, thinking and reasoning skills.

The Pitt team — including senior author Koldamova, first author Nicholas Fitz and co-authors Iliya Lefterov and Andrea Cronican — was studying Alzheimer's when the Case Western Reserve report was released. The team decided to employ different experiments to independently confirm the findings.

Researchers dropped healthy mice into a pool of water with a small platform just under the surface and timed how long it took the mice to find the platform, Fitz said. Healthy mice averaged 40 seconds on the first try, then steadily improved their times in subsequent tests, eventually finding the platform in 10 seconds. The mice were learning, Fitz said. They were remembering the location of and finding the platform.

Mice exhibiting Alzheimer's symptoms, however, did not improve their times.

“It was more like a random chance of them finding the platform,” he said. “They did not learn the strategy.”

Researchers then treated the mice with bexarotene and their times improved as rapidly as those of the healthy mice, he said.

The results offer hope to people afflicted with the devastating disease, said Clay Jacobs, vice president of programs and services for the Alzheimer's Association Greater Pennsylvania Chapter.

“These studies are so important because they provide direction and focus. While not necessarily being the answer, they help guide the path researchers take in moving forward,” Jacobs said. “It's fantastic. Any new knowledge that comes out of new research is helpful.”

Other tests showed that mice with Alzheimer's treated with the anti-cancer drug improved long-term memory and recognition functions to levels shown by the healthy mice, Koldamova and Fitz said.

“It's a good sign,” Fitz said. “It's definitely not the end-all, but it's a direction that needs to be further explored as a possible route of treatment.”

Such studies not only push researchers closer to finding a cure, they cause a buzz that, ideally, involves more people and increases funding for research, Jacobs said.

“There is reason to hope,” he said. “Even research trials that fail enhance our knowledge of the disease. ... People are talking about Alzheimer's so much more frequently now (than) even 20 years ago. This is an opportunity for hope, but also an opportunity to educate ourselves.”

Officials did not know when human trials might begin.

Research must determine side effects and other issues stemming from treatment on humans, Fitz said. The bexarotene treatment did not affect the weight or general behavior of the mice, and it was equally effective in male and female mice.

The Pitt team's research was funded by the National Institutes of Health's National Institute on Aging and the Alzheimer's Association.

Chris Togneri is a staff writer for Trib Total Media. He can be reached at 412-380-5632 or ctogneri@tribweb.com.

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