Triangle Alzheimer’s experts hope cancer drug helps March 13, 2012 

New research released today focuses on potential use of a cancer drug in reducing tangles in the brain and improving cognition among people with Alzheimer’s, in a glimmer of hope for dementia patients and families.

Concentrating on tangles that affect brain cells is part of a trend toward treatments that could halt memory loss and improve cognition among dementia patients, according to Triangle experts.

Dr. Murali Doraiswamy of Duke University Medical Center and Dr. Dan Kaufer of the University of North Carolina-Chapel Hill commented on an article published Tuesday in The Journal of Neuroscience. The results of research by Kurt Brunden and colleagues at the University of Pennsylvania, the article details promising results on older laboratory mice treated with epothilone D (EpoD), a cancer drug which progressed to a second phase of clinical trials.

The drug reduced levels of tangles, or tau protein, in mouse brains, slowing neurological damage and improving brain function. Many earlier studies in the past decade had focused on treating plaque, the sticky protein also found on the brains of people with Alzheimer’s.

“We need to start developing a repertoire of drugs aimed at the tangles,” Doraiswamy said. “We have also known that the tangles are highly collaborative with memory functions. “The odds of such a drug improving cognition are quite high.

“If you can find a drug that is already cleared for another application, it would be relatively easy to get it cleared for human trials.”

According to the nonprofit Alzheimer’s NC, the disease affects more than 140,000 people in the state, a number projected to quadruple by 2025 with the aging of the baby boomer demographic bulge. For the increasing thousands of patients and families, the disease has meant a sentence to years of gradual loss of memory and ability to function, taking a toll both on people with the Alzheimer’s and their caregivers.

Both Doraiswamy and Kaufer said the results of the University of Pennsylvania research are significant, but noted that it’s impossible to say when the former cancer rug will translate into a treatment for humans.

“If you were a genetically engineered mouse, we have half a dozen methods that can cure you, you wouldn’t have anything to worry about,” said Kaufer, director of the UNC Memory Disorders Program.

“But nothing has translated to the human condition. It’s a big jump.”

However, Kaufer said, the research is in line with most recent thinking about Alzheimer’s, which shows that the disease can develop for 10 to 15 years without showing noticeable symptoms.

“It shifts us from focusing on people who have Alzheimer’s disease to trying to identify treatments that are effective on people who are earlier on the process,” Kaufer said. “This points us in the direction that we want to go.”

The researchers at Penn gave EpoD weekly to older Alzheimer’s model mice for three months before evaluating them. They found reduced formation of tangles in the brain and improved performance in learning and memory tests. The treated mice were compared with a test group that did not receive the drug.

“These results suggest that EpoD might have therapeutic benefit in Alzheimer’s disease and related neurodegenerative diseases, such as frontotemporal lobar degeneration, where abnormal tau tangles are present,” Brunden said in a news release.

An important difference in EpoD with other treatments that have shown results in younger mice is its ability to cross the blood barrier, “the network of blood vessels that keeps potentially harmful molecules from entering the brain,” the statement said.

Inability to cross that barrier has meant the end for other promising treatments.

“This is a new framework,” Kaufer said. “It doesn’t really impact what we do clinically now, but it sets the agenda.

“One day we’re going to hit a home run.”

Goldsmith: 919-829-8929

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