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Tobacco derivative shows promise in Alzheimer's study

TAMPA — Smoking is the biggest preventable cause of death, but University of South Florida researchers believe a substance produced from tobacco leaves could stave off another killer, Alzheimer's disease.

Mice bred to develop dementia were given cotinine, a compound derived from tobacco. They performed better on memory tests than similar mice that didn't receive the substance. And they had fewer of the brain plaques associated with Alzheimer's, according to a study led by researchers at USF and the Bay Pines VA Healthcare System.

"The cotinine prevented the memory loss. That was the striking discovery," said lead researcher Valentina Echeverria Moran. "Taking cotinine when the first symptoms of the pathology arrive maybe could prevent the appearance of memory loss."

But experts cautioned that the research, now available online in the Journal of Alzheimer's Disease, remains a long way from helping the 5.4 million Americans who have the disease.

Dozens of substances seem to slow or stop memory loss in dementia mice, as well as alter brain biology. But so far, none has succeeded enough in human trials to gain FDA approval as a treatment.

At USF alone, the cotinine study marks the fourth time in two years that researchers have published promising results involving mice. Caffeine seemed to help, too, as did a protein called Leukine and high doses of electromagnetic radiation like that produced by cell phones.

Yet currently, medicines for people with Alzheimer's can do little more than temporarily boost brainpower. Nothing has yet halted brain cell deterioration — or even slowed the disease down.

Still, the cotinine study is intriguing because it might help explain conflicting theories about smoking, nicotine and Alzheimer's, said Dr. Mary Carrillo, a senior director at the national Alzheimer's Association.

Though early studies indicated that smoking might reduce the chance of getting Alzheimer's, later epidemiological work indicated the opposite — that smoking leads to more dementia, Carrillo said. Yet nicotine in lab dishes, rather than nicotine delivered through smoking, seemed to have a beneficial effect.

Nicotine is addictive and toxic, which makes it a poor candidate for therapeutic use in humans. But when the body breaks it down, more than 80 percent turns into cotinine, which lingers longer in the body and has few harmful effects.

Using a component part of nicotine "and seeing a protective effect in mice is a very interesting signal," Carrillo said. "This is worth pursuing."

The USF-Bay Pines researchers used mice genetically engineered to develop Alzheimer's-like symptoms. Some of the mice were fed cotinine beginning at the age of 2 months — the human equivalent of young adulthood. That's when these mice typically start to develop dementia. The cotinine feedings lasted for 3 1/2 months.

Then the mice went swimming.

In a water maze, the mice swam around until they found a submerged platform where they could escape. Alzheimer's mice generally have a hard time remembering where to go. But those that received cotinine performed better than those that received no treatment.

The monthlong battery of tests continued out of the water at a circular maze with 16 holes around the periphery. The mice had to find the hole through which they could escape bright light and fan winds.

Again, the cotinine-treated mice showed fewer signs of memory loss.

After the experiments concluded, researchers sliced into the brains of their mice and found the treated animals had a significant reduction in amyloid plaques.

They also found fewer of the sticky substances that create the plaques. Researchers speculate that these dual benefits — enhanced memory and reduced amyloid — could mean cotinine will prove more successful than treatments with only one impact.

Echeverria Moran, a research chemist at Bay Pines and associate professor at USF, said the next step is to secure $1 million in funding to conduct a clinical trial in people. She wants to test cotinine in people with mild cognitive impairment, the beginning signs of Alzheimer's. Scientists increasingly believe that early intervention may be the best hope for treating the disease, which may actually start a decade or more before symptoms are seen.

Funding for the mouse research came from the Florida Department of Health, the national Alzheimer's Association, USF and the Veterans Affairs Department.

"I cannot assure you that it will be the cure for Alzheimer's, but I think it's worth it to try," she said. "I'm excited because I know my drug is not toxic and therefore will not be any harm. The only thing that can be done is good."

Letitia Stein can be reached at lstein@sptimes.com or (813) 226-3322. Stephen Nohlgren can be reached at nohlgren@sptimes.com.

Tobacco derivative shows promise in Alzheimer's study 04/27/11 [Last modified: Wednesday, April 27, 2011 10:17pm]

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