Promising Alzheimer's drug boosts toxic protein

A split-view image showing PET scans of a normal brain (L) and a brain with Alzheimer's disease.

CHICAGO (Reuters) - Dimebon, Medivation Inc's promising experimental Alzheimer's drug, significantly raised levels of a toxic protein in the brains of mice, yet has been shown to delay thinking problems in human dementia patients, U.S. researchers said on Wednesday.

"This is an unexpected result," said Dr. Samuel Gandy, a researcher at Mount Sinai School of Medicine in New York, whose findings were presented at an Alzheimer's meeting in Vienna.

The study raises new questions about how the drug works and new worries about drugs meant to remove telltale clumps of a protein called beta amyloid from the brain as a way to reverse Alzheimer's disease.

Researchers are not sure whether amyloid is a cause or a symptom of Alzheimer's but, either way, getting rid of it had appeared to be a good thing.

"We think we want amyloid levels to go down," Gandy said in a telephone interview. "Here is this compound that is looking very promising clinically that is making amyloid levels go up."

Dimebon, first sold in Russia as an antihistamine, is being developed jointly with Pfizer Inc, maker of the Alzheimer's drug Aricept.

Researchers see Dimebon as the best hope for a new treatment for the incurable, mind-robbing disease that affects 26 million people globally.

Now in late-stage testing, Dimebon seems to delay thinking problems in people but it is not clear how.

"We wanted to know what Dimebon was doing to amyloid," Gandy said.

His team tested mice genetically engineered to have a human form of Alzheimer's. The drug increased amyloid outside nerve cells.

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"It certainly means this medicine is not acting by an acute amyloid-lowering effect, which is what we were looking for in the lab," Gandy said.

Separately, Israeli researchers reported promising results from a study in mice that takes aim at a less-studied brain protein called tau, which is strongly associated with dementia in Alzheimer's disease.

Hanna Rosenmann of Hadassah University Hospital in Jerusalem and colleagues found that injecting mice with tau-fighting antibodies reduced the number of tangles in the brain by 40 percent and produced tau antibodies in the blood.

"That looks to me like a viable therapeutic avenue," said Dr. Gary Kennedy of Montefiore Medical Center in New York.

The "amyloid hypothesis" has already produced some stunning failures in large, late-stage trials. They include a drug by Canadian biotech Bellus Health, formerly known as Neurochem Inc, and one last year with Flurizan, dealing a blow to its backers Myriad Genetics and Lundbeck.

"You have to wonder if maybe we have been thinking about this wrong," Gandy said.

And he wonders about bapineuzumab, a highly watched drug for Alzheimer's being developed by Wyeth and Irish drugmaker Elan Corp and Johnson & Johnson. Last year, the drug failed to meet its primary goal in a mid-stage trial and caused brain swelling at higher doses.

Gandy said Dimebon could be making nerve cells more efficient at excreting the toxic protein. Or perhaps the drug has such a powerful effect that it overrides any harm being done to the brain by beta amyloid.

(Editing by Maggie Fox and John O'Callaghan)